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Regenerating (Reg) Gene Family

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Animal Lectins: Form, Function and Clinical Applications

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Abstract

Regenerating (Reg) gene is a multigene super-family grouped into four subclasses, types I, II, III, and IV based on the primary structures of the encoded proteins and represents the products of small secretory proteins, which can function as acute phase reactants, lectins, antiapoptotic factors or growth factors for pancreatic β-cells, neural cells and epithelial cells in the digestive system. Among C-type lectin gene superfamily, the Reg-related genes are classified in group VII and encode small secreted proteins with a single carbohydrate recognition domain linked to a short N-terminal peptide (Drickamer 1999; Zhang et al. 2003a). The genes coding these proteins are tandemly clustered on chromosome 2p12 in humans and may have arisen from the same ancestral gene by gene duplication. The expression of this group of proteins is controlled by complex mechanisms, some members being constitutively expressed in certain tissues while, in others, they require activation by several factors. These members have several apparently unrelated biological effects, depending on the member studied and the target cell. insoluble fibrils at physiological pH (Iovanna and Dagorn 2005).

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References

  • Abe M, Nata K, Akiyama T et al (2000) Identification of a novel Reg family gene, Reg-IIIdelta, and mapping of all three types of Reg family gene in a 75 kilobase mouse genomic region. Gene 246:111–122

    Article  PubMed  CAS  Google Scholar 

  • Abergel C, Chenivesse S, Stinnakre MG et al (1999) Crystallization and preliminary crystallographic study of HIP/PAP, a human C-lectin overexpressed in primary liver cancers. Acta Crystallogr D Biol Crystallogr 55:1487–1489

    Article  PubMed  CAS  Google Scholar 

  • Akiyama T, Takasawa S, Nata K et al (2001) Activation of Reg gene, a gene for insulin-producing β -cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation. Proc Natl Acad Sci USA 98:48–53

    PubMed  CAS  Google Scholar 

  • Ampo K, Suzuki A, Konishi H et al (2009) Induction of pancreatitis-associated protein (PAP) family members in neurons after traumatic brain injury. J Neurotrauma 26:1683–1693

    Article  PubMed  Google Scholar 

  • Apte MV, Norton ID et al (1996) Both ethanol and protein deficiency increase messenger RNA levels for pancreatic lithostathine. Life Sci 58:485–492

    Article  PubMed  CAS  Google Scholar 

  • Asahara M, Mushiake S, Shimada S et al (1996) Reg gene expression is increased in rat gastric enterochromaffin-like cells following water immersion stress. Gastroenterology 111:45–55

    Article  PubMed  CAS  Google Scholar 

  • Astrosini C, Roeefzaad C, Dai YY et al (2008) REG 1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis. Int J Cancer 123:409–413

    Article  PubMed  CAS  Google Scholar 

  • Averill S, Davis DR et al (2002) Dynamic pattern of Reg-2 expression in rat sensory neurons after peripheral nerve injury. J Neurosci 22:7493–7501

    PubMed  CAS  Google Scholar 

  • Averill S, Inglis JJ et al (2008) Reg-2 expression in dorsal root ganglion neurons after adjuvant-induced monoarthritis. Neuroscience 155:1227–1236

    Article  PubMed  CAS  Google Scholar 

  • Baeza N, Sanchez D, Vialettes B et al (1997) Specific Reg II gene overexpression in the non-obese diabetic mouse pancreas during active diabetogenesis. FEBS Lett 416:364–368

    Article  PubMed  CAS  Google Scholar 

  • Baeza N, Sanchez D, Christa L et al (2001) Pancreatitis-associated protein (HIP/PAP) gene expression is upregulated in NOD mice pancreas and localized in exocrine tissue during diabetes. Digestion 64:233–9

    Article  PubMed  CAS  Google Scholar 

  • Barbosa H, Bordin S, Stoppiglia L et al (2006) Islet neogenesis associated protein (INGAP) modulates gene expression in cultured neonatal rat islets. Regul Pept 136:78–84

    Article  PubMed  CAS  Google Scholar 

  • Barbosa HC, Bordin S, Anhê G et al (2008) Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway. J Endocrinol 199:299–306

    Article  PubMed  CAS  Google Scholar 

  • Barthet M, Dubucquoy L, Garcia S et al (2003) Pancreatic changes in TNBS-induced colitis in mice. Gastroenterol Clin Biol 27:895–900

    PubMed  Google Scholar 

  • Bartoli C, Dagorn JC, Fontes M et al (1995) A limited genomic region contains the human REG and REG-related genes. Eur J Hum Genet 3:344–350

    PubMed  CAS  Google Scholar 

  • Bartoli C, Baeza N, Figarella C et al (1998) Expression of peptide-23/pancreatitis-associated protein and Reg genes in human pituitary and adenomas: comparison with other fetal and adult human tissues. J Clin Endocrinol Metab 83:4041–4046

    Article  PubMed  CAS  Google Scholar 

  • Bernard JP, Adrich Z, Montalto G et al (1991) Immunoreactive forms of pancreatic stone protein in six mammalian species. Pancreas 6:162–167

    Article  PubMed  CAS  Google Scholar 

  • Bernard JP, Adrich Z, Montalto G et al (1992) Inhibition of nucleation and crystal growth of calcium carbonate by human lithostathine. Gastroenterology 103:1277–1284

    PubMed  CAS  Google Scholar 

  • Bernard JP, Barthet M, Gharib B et al (1995) Quantification of human lithostathine by high performance liquid chromotography. Gut 36:630–636

    Article  PubMed  CAS  Google Scholar 

  • Bernard-Perrone FR, Renaud WP, Guy-Crotte OM et al (1999) Expression of REG protein during cell growth and differentiation of two human colon carcinoma cell lines. J Histochem Cytochem 47:863–870

    Article  PubMed  CAS  Google Scholar 

  • Bertrand JA, Pignol D, Bernard JP et al (1996) Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. EMBO J 15:2678–2684

    PubMed  CAS  Google Scholar 

  • Bimmler D, Graf R, Scheele GA et al (1997) Pancreatic stone protein (lithostathine), a physiologically relevant pancreatic calcium carbonate crystal inhibitor? J Biol Chem 272:3073–3082

    Article  PubMed  CAS  Google Scholar 

  • Bimmler D, Angst E et al (1999) Regulation of PSP/Reg in rat pancreas: immediate and steady-state adaptation to different diets. Pancreas 19:255–267

    Article  PubMed  CAS  Google Scholar 

  • Bimmler D, Schiesser M, Perren A et al (2004) Coordinate regulation of PSP/Reg and PAP-Isoforms as a family of secretory stress proteins in an animal model of chronic pancreatitis. J Surg Res 118:122–135

    Article  PubMed  CAS  Google Scholar 

  • Bishnupuri KS, Luo Q, Korzenik JR et al (2006a) Dysregulation of Reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes. Cancer Biol Ther 5:1714–1720

    Article  PubMed  CAS  Google Scholar 

  • Bishnupuri KS, Luo Q, Murmu N et al (2006b) Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas. Gastroenterology 130:137–149

    Article  PubMed  CAS  Google Scholar 

  • Bishnupuri KS, Luo Q, Sainathan SK et al (2010) Reg IV regulates normal intestinal and colorectal cancer cell susceptibility to radiation-induced apoptosis. Gastroenterology 138:616–626

    Article  PubMed  CAS  Google Scholar 

  • Blennow K, Wallin A, Chong JK (1995) Cerebrospinal fluid ‘neuronal thread protein’ comes from serum by passage over the blood–brain barrier. Neurodegeneration 4:187–193

    Article  PubMed  CAS  Google Scholar 

  • Bluth MH, Patel SA, Dieckgraefe BK et al (2006) Pancreatic regenerating protein (Reg I) and Reg I receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis. World J Gastroenterol 12:4511–4516

    PubMed  CAS  Google Scholar 

  • Bluth M, Mueller CM, Pierre J et al (2008) Pancreatic regenerating protein I in chronic pancreatitis and aging: implications for new therapeutic approaches to diabetes. Pancreas 37:386–395

    Article  PubMed  Google Scholar 

  • Bodeker H, Fiedler F et al (1998) Pancreatitis-associated protein is upregulated in mouse pancreas during acute pancreatitis. Digestion 59:186–191

    Article  PubMed  CAS  Google Scholar 

  • Bodeker H, Keim V, Fiedler F et al (1999) PAP-I interacts with itself, PAP-II, PAP-III, and lithostathine/RegIα. Mol Cell Biol Res Commun 2:150–154

    Article  PubMed  CAS  Google Scholar 

  • Borelli MI, Del Zotto H, Flores LE et al (2007) Transcription, expression and tissue binding in vivo of INGAP and INGAP-related peptide in normal hamsters. Regul Pept 140:192–197

    Article  PubMed  CAS  Google Scholar 

  • Cai L, Harris WR, Marshak DR et al (1990) Structural analysis of bovine pancreatic thread protein. J Protein Chem 9:623–632

    Article  PubMed  CAS  Google Scholar 

  • Cao G, Ma J, Zhang Y et al (2009) Pancreatitis-associated protein is related closely to neoplastic proliferative activity in patients with colorectal carcinoma. Anat Rec (Hoboken) 292:249–253

    Article  CAS  Google Scholar 

  • Carroccio A, Iovanna JL, Iacono G et al (1997) Pancreatitis-associated protein in patients with celiac disease: serum levels and immunocytochemical localization in small intestine. Digestion 58:98–103

    Article  PubMed  CAS  Google Scholar 

  • Cash HL, Whitham CV, Behrendt CL et al (2006a) Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313:1126–1130

    Article  PubMed  CAS  Google Scholar 

  • Cash HL, Whitham CV, Hooper LV (2006b) Refolding, purification, and characterization of human and murine Reg-III proteins expressed in Escherichia coli. Protein Expr Purif 48:151–159

    Article  PubMed  CAS  Google Scholar 

  • Cavard C, Terris B, Grimber G et al (2006) Overexpression of regenerating islet-derived 1 α and 3 α genes in human primary liver tumors with β-catenin mutations. Oncogene 25:599–608

    Article  PubMed  CAS  Google Scholar 

  • Cerini C, Peyrot V, Garnier C et al (1999) Biophysical characterization of lithostathine. Evidences for a polymeric structure at physiological pH and a proteolysis mechanism leading to the formation of fibrils. J Biol Chem 274:22266–22274

    Article  PubMed  CAS  Google Scholar 

  • Cerwenka H, Aigner R, Bacher H et al (2001) Pancreatitis-associated protein (PAP) in patients with pancreatic cancer. Anticancer Res 21:1471–1474

    PubMed  CAS  Google Scholar 

  • Chakraborty C, Katsumata N, Myal Y et al (1995a) Age-related changes in peptide-23/pancreatitis-associated protein and pancreatic stone protein/Reg gene expression in the rat and regulation by growth hormone-releasing hormone. Endocrinology 136:1843–1849

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty C, Sharma S, Katsumata N et al (1995b) Plasma clearance, tissue uptake and expression of pituitary peptide 23/pancreatitis-associated protein in the rat. J Endocrinol 145:461–469

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty C, Vrontakis M, Molnar P et al (1995c) Expression of pituitary peptide 23 in the rat uterus: regulation by estradiol. Mol Cell Endocrinol 108:149–154

    Article  PubMed  CAS  Google Scholar 

  • Chen CY, Lin XZ, Wu HC et al (2005) The value of biliary amylase and hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I (HIP/PAP-I) in diagnosing biliary malignancies. Clin Biochem 38:520–525

    Article  PubMed  CAS  Google Scholar 

  • Chinuki D, Amano Y, Ishihara S et al (2008) REG Iα protein expression in Barrett’s esophagus. J Gastroenterol Hepatol 23:296–302

    Article  PubMed  CAS  Google Scholar 

  • Choi B, Suh Y, Kim WH et al (2007) Downregulation of regenerating islet-derived 3 α (REG3Α) in primary human gastric adenocarcinomas. Exp Mol Med 39:796–804

    Article  PubMed  CAS  Google Scholar 

  • Christa L, Felin M, Morali O et al (1994) The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity. FEBS Lett 337:114–118

    Article  PubMed  CAS  Google Scholar 

  • Christa L, Carnot F, Simon MT et al (1996) HIP/PAP-is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells. Am J Physiol 271:G993–G1002

    PubMed  CAS  Google Scholar 

  • Christa L, Simon M-T, Brezault-Bonnet C et al (1999) Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) is expressed and secreted by proliferating ductules as well as by hepatocarcinoma and cholangiocarcinoma cells. Am J Pathol 155:1525–1533

    Article  PubMed  CAS  Google Scholar 

  • Christa L, Pauloin A et al (2000) High expression of the human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein (HIP/PAP) gene in the mammary gland of lactating transgenic mice. Secretion into the milk and purification of the HIP/PAP lectin. Eur J Biochem 267:1665–1671

    Article  PubMed  CAS  Google Scholar 

  • Christofilis MA, Carrere J, Atlan-Gepner C et al (1999) Serum Reg protein level is not related to the β cell destruction/regeneration process during early phases of diabetogenesis in type I diabetes. Eur J Endocrinol 141:368–373

    Article  PubMed  CAS  Google Scholar 

  • Closa D, Motoo Y, Iovanna JL (2007) Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine. World J Gastroenterol 13:170–174

    PubMed  CAS  Google Scholar 

  • Cui W, De Jesus K, Zhao H et al (2009) Overexpression of REG3α increases cell growth and the levels of cyclin D1 and CDK4 in insulinoma cells. Growth Factors 27:195–202

    Article  PubMed  CAS  Google Scholar 

  • Davies PL, Hew CL (1990) Biochemistry of fish antifreeze proteins. FASEB J 4:2460–2468

    PubMed  CAS  Google Scholar 

  • De Caro A, Multigner L, Dagorn JC, Sarles H (1988) The human pancreatic stone protein. Biochimie 70:1209–1214

    Article  PubMed  Google Scholar 

  • De Caro AM, Adrich Z, Fournet B et al (1989) N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue. Biochim Biophys Acta 994:281–284

    Article  PubMed  Google Scholar 

  • de la Monte SM, Wands JR (2004) Alzheimer-associated neuronal thread protein mediated cell death is linked to impaired insulin signaling. J Alzheimers Dis 6:231–242

    PubMed  Google Scholar 

  • de la Monte SM, Ozturk M, Wands JR (1990) Enhanced expression of an exocrine pancreatic protein in Alzheimer’s disease and the developing human brain. J Clin Invest 86:1004–1013

    Article  PubMed  Google Scholar 

  • de La Monte SM, Carlson RI, Brown NV, Wands JR (1996a) Profiles of neuronal thread protein expression in Alzheimer’s disease. J Neuropathol Exp Neurol 55:1038–1050

    Google Scholar 

  • de la Monte SM, Xu YY, Wands JR (1996b) Modulation of neuronal thread protein expression with neuritic sprouting: relevance to Alzheimer’s disease. J Neurol Sci 138:26–35

    Article  PubMed  Google Scholar 

  • de la Monte SM, Garner W, Wands JR (1997) Neuronal thread protein gene modulation with cerebral infarction. J Cereb Blood Flow Metab 17:623–635

    Article  PubMed  Google Scholar 

  • de la Monte SM, Chen GJ, Rivera E, Wands JR (2003) Neuronal thread protein regulation and interaction with microtubule-associated proteins in SH-Sy5y neuronal cells. Cell Mol Life Sci 60:2679–2691

    Article  PubMed  CAS  Google Scholar 

  • De Reggi M, Gharib B (2001) Protein-X, pancreatic stone-, pancreatic thread-, reg-protein, P19, lithostathine, and now what? Characterization, structural analysis and putative function(s) of the major non-enzymatic protein of pancreatic secretions. Curr Protein Pept Sci 2:19–42

    Article  PubMed  Google Scholar 

  • De Reggi M, Capon C, Gharib B et al (1995) The glycan moiety of human pancreatic lithostathine. Structure characterization and possible pathophysiological implications. Eur J Biochem 230:503–510

    Article  PubMed  Google Scholar 

  • De Reggi M, Gharib B, Patard L, Stoven V (1998) Lithostathine, the presumed pancreatic stone inhibitor, does not interact specifically with calcium carbonate crystals. J Biol Chem 273:4967–4971

    Article  PubMed  Google Scholar 

  • Del Zotto H, Massa L, Rafaeloff R et al (2000) Possible relationship between changes in islet neogenesis and islet neogenesis-associated protein-positive cell mass induced by sucrose administration to normal hamsters. J Endocrinol 165:725–733

    Article  PubMed  Google Scholar 

  • Demaugre F, Philippe Y, Sar S et al (2004) HIP/PAP, a C-type lectin overexpressed in hepatocellular carcinoma, binds the RII α regulatory subunit of cAMP-dependent protein kinase and alters the cAMP-dependent protein kinase signaling. Eur J Biochem 271:3812–3820

    Article  PubMed  CAS  Google Scholar 

  • Desjeux A, Barthet M, Barthellemy S et al (2002) Serum measurements of pancreatitis associated protein in active Crohn’s disease with ileal location. Gastroenterol Clin Biol 26:23–28

    PubMed  CAS  Google Scholar 

  • Dhar DK, Udagawa J, Ishihara S et al (2004) Expression of regenerating gene I in gastric adenocarcinomas: correlation with tumor differentiation status and patient survival. Cancer 100:1130–1136

    Article  PubMed  CAS  Google Scholar 

  • Dieckgraefe BK, Crimmins DL, Landt V et al (2002) Expression of the regenerating gene family in inflammatory bowel disease mucosa: Reg Iα upregulation, processing, and antiapoptotic activity. J Investig Med 50:421–434

    Article  PubMed  CAS  Google Scholar 

  • Drickamer K (1992) Engineering galactose-binding activity into a C-type mannose binding protein. Nature 360:183–186

    Article  PubMed  CAS  Google Scholar 

  • Drickamer K (1999) C-type lectin-like domains. Curr Opin Struct Biol 9:585–590

    Article  PubMed  CAS  Google Scholar 

  • Duplan L, Michel B, Boucraut J et al (2001) Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer’s disease. Neurobiol Aging 22:79–88

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Frigerio JM, Dagorn JC et al (1993a) Rapid PCR cloning and sequence determination of the rat lithostathine gene. Biochim Biophys Acta 1174:99–102

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Frigerio JM, Keim V et al (1993b) Structural organization of the gene encoding the rat pancreatitis-associated protein. Analysis of its evolutionary history reveals an ancient divergence from the other carbohydrate-recognition domain-containing genes. J Biol Chem 268:14470–14475

    PubMed  CAS  Google Scholar 

  • Dusetti NJ, Frigerio JM, Fox MF et al (1994a) Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene. Genomics 19:108–114

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Mallo G, Dagorn JC, Iovanna JL (1994b) Serum from rats with acute pancreatitis induces expression of the PAP mRNA in the pancreatic acinar cell line AR-42J. Biochem Biophys Res Commun 204:238–243

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Frigerio JM, Szpirer C et al (1995a) Cloning, expression and chromosomal localization of the rat pancreatitis-associated protein III gene. Biochem J 307:9–16

    PubMed  CAS  Google Scholar 

  • Dusetti NJ, Ortiz EM, Mallo GV et al (1995b) Pancreatitis-associated protein I (PAP I), an acute phase protein induced by cytokines. Identifi cation of two functional interleukin-6 response elements in the rat PAP I promoter region. J Biol Chem 270:22417–22421

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Mallo GV, Ortiz EM et al (1996a) Induction of lithostathine/Reg mRNA expression by serum from rats with acute pancreatitis and cytokines in pancreatic acinar AR-42 J cells. Arch Biochem Biophys 330:129–132

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Montalto G et al (1996b) Mechanism of PAP-I gene induction during hepatocarcinogenesis: clinical implications. Br J Cancer 74:1767–1775

    Article  PubMed  CAS  Google Scholar 

  • Dusetti NJ, Vasseur S, Ortiz EM et al (1997) The pancreatitis-associated protein I promoter allows targeting to the pancreas of a foreign gene, whose expression is up-regulated during pancreatic inflammation. J Biol Chem 272:5800–5804

    Article  PubMed  CAS  Google Scholar 

  • Ewart KV, Rubinsky B, Fletcher GL (1992) Structural and functional similarity between fish antifreeze proteins and calciumdependant lectins. Biochem Biophys Res Comm 185:335–340

    Article  PubMed  CAS  Google Scholar 

  • Fang M, Huang JY, Ling SC et al (2010) Effects of Reg-2 on survival of spinal cord neurons in vitro. Anat Rec (Hoboken) 293:464–476

    Article  CAS  Google Scholar 

  • Ferrés-Masó M, Sacilotto N, López-Rodas G et al (2009) PAP-I signaling involves MAPK signal transduction. Cell Mol Life Sci 66:2195–2204

    Article  PubMed  CAS  Google Scholar 

  • Fiedler F, Croissant N, Rehbein C et al (1998) Acute-phase response of the rat pancreas protects against further aggression with severe necrotizing pancreatitis. Crit Care Med 26:887–894

    Article  PubMed  CAS  Google Scholar 

  • Flores LE, GarcÃa ME, Borelli MI et al (2003) Expression of islet neogenesis-associated protein in islets of normal hamsters. J Endocrinol 177:243–248

    Article  PubMed  CAS  Google Scholar 

  • Folch-Puy E, GarcÃa-Movtero A et al (2003) The pancreatitis-associated protein induces lung inflammation in the rat through activation of TNFα expression in hepatocytes. J Pathol 199:398–408

    Article  PubMed  CAS  Google Scholar 

  • Folch-Puy E, Granell S, Dagorn JC et al (2006) Pancreatitis-associated protein I suppresses NF-kappa B activation through a JAK/STAT-mediated mechanism in epithelial cells. J Immunol 176:3774–3779

    PubMed  CAS  Google Scholar 

  • Frigerio JM, Dusetti NJ, Garrido P et al (1993a) The pancreatitis associated protein III (PAP-III), a new member of the PAP gene family. Biochim Biophys Acta 1216:329–331

    Article  PubMed  CAS  Google Scholar 

  • Frigerio JM, Dusetti NJ, Keim V et al (1993b) Identification of a second rat pancreatitis-associated protein. Messenger RNA cloning, gene structure, and expression during acute pancreatitis. Biochemistry 32:9236–9241

    Article  PubMed  CAS  Google Scholar 

  • Fu K, Sarras MP Jr, De Lisle RC, Andrews GK (1996) Regulation of mouse pancreatitis-associated protein-I gene expression during caerulein-induced acute pancreatitis. Digestion 57:333–340

    Article  PubMed  CAS  Google Scholar 

  • Fukuhara H, Kadowaki Y, Ose T et al (2010) In vivo evidence for the role of RegI in gastric regeneration: transgenic overexpression of RegI accelerates the healing of experimental gastric ulcers. Lab Invest 90:556–565

    Article  PubMed  CAS  Google Scholar 

  • Fukui H, Kinoshita Y, Maekawa T et al (1998) Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats. Gastroenterology 115:1483–1493

    Article  PubMed  CAS  Google Scholar 

  • Fukui H, Franceschi F, Penland RL et al (2003) Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in Mongolian gerbils. Lab Invest 83:1777–1786

    Article  PubMed  CAS  Google Scholar 

  • Fukui H, Fujii S, Takeda J et al (2004) Expression of Reg Iα protein in human gastric cancers. Digestion 69:177–184

    Article  PubMed  CAS  Google Scholar 

  • Funakoshi A, Miyasaka K, Jimi A et al (1995) Changes in gene expression of pancreatitis-associated protein and pancreatic secretory trypsin inhibitors in experimental pancreatitis produced by pancreatic duct occlusion in rats: comparison with gene expression of cholecystokinin and secretin. Pancreas 11:147–153

    Article  PubMed  CAS  Google Scholar 

  • Gagliardino JJ, Del Zotto H, Massa L et al (2003) Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors. J Endocrinol 177:249–259

    Article  PubMed  CAS  Google Scholar 

  • Geider S, Baronnet A, Cerini C et al (1996) Pancreatic lithostathine as a calcite habit modifier. J Biol Chem 271:26302–26306

    Article  PubMed  CAS  Google Scholar 

  • Geng J, Fan J, Wang P et al (2009) REG 1A predicts recurrence in stage Ta/T1 bladder cancer. Eur J Surg Oncol 35:852–857

    Article  PubMed  CAS  Google Scholar 

  • Gerbaud V, Pignol D, Loret E et al (2000) Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine. J Biol Chem 275:1057–1064

    Article  PubMed  CAS  Google Scholar 

  • Gharib B, Fox MF, Bartoli C et al (1993) Human regeneration protein/lithostathine genes map to chromosome 2p12. Ann Hum Genet 57:9–16

    Article  PubMed  CAS  Google Scholar 

  • Giorgi D, Bernard JP, Rouquier S et al (1989) Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis. J Clin Invest 84:100–106

    Article  PubMed  CAS  Google Scholar 

  • Gironella M, Iovanna JL et al (2005) Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease. Gut 54:1244–1253

    Article  PubMed  CAS  Google Scholar 

  • Gironella M, Folch-Puy E, LeGoffic A et al (2007) Experimental acute pancreatitis in PAP/HIP knock-out mice. Gut 56:1091–1097

    Article  PubMed  CAS  Google Scholar 

  • Graf R, Schiesser M, Scheele GA et al (2001) A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. J Biol Chem 276:21028–21038

    Article  PubMed  CAS  Google Scholar 

  • Graf R, Schiesser M, Reding T et al (2006) Exocrine meets endocrine: pancreatic stone protein and regenerating protein–two sides of the same coin. J Surg Res 133:113–120

    Article  PubMed  CAS  Google Scholar 

  • Grégoire C, Marco S, Thimonier J et al (2001) Three-dimensional structure of the lithostathine protofibril, a protein involved in Alzheimer’s disease. EMBO J 20:3313–3321

    Article  PubMed  Google Scholar 

  • Grønborg M, Bunkenborg J, Kristiansen TZ et al (2004) Comprehensive proteomic analysis of human pancreatic juice. J Proteome Res 3:1042–1055

    Article  PubMed  CAS  Google Scholar 

  • Gross J, Brauer AW, Bringhurst RF et al (1985a) An unusual bovine pancreatic protein exhibiting pH-dependent globule-fibril transformation and unique amino acid sequence. Proc Natl Acad Sci USA 82:5627–5631

    Article  PubMed  CAS  Google Scholar 

  • Gross J, Carlson RI, Brauer AW et al (1985b) Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. J Clin Invest 76:2115–2126

    Article  PubMed  CAS  Google Scholar 

  • Gross DJ, Weiss L, Reibstein I et al (1998) Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment. Endocrinology 139:2369–2374

    Article  PubMed  CAS  Google Scholar 

  • Gu Z, Rubin MA, Yang Y et al (2005) Reg IV: a promising marker of hormone refractory metastatic prostate cancer. Clin Cancer Res 1:2237–2243

    Article  Google Scholar 

  • Guo Y, Xu J, Li N, Gao F, Huang P (2010) RegIV potentiates colorectal carcinoma cell migration and invasion via its CRD domain. Cancer Genet Cytogenet 199:38–44

    Article  PubMed  CAS  Google Scholar 

  • Gurr W, Yavari R, Wen L et al (2002) A Reg family protein is overexpressed in islets from a patient with new-onset type 1 diabetes and acts as T-cell autoantigen in NOD mice. Diabetes 51:339–346

    Article  PubMed  CAS  Google Scholar 

  • Gurr W, Shaw M, Li Y, Sherwin R (2007) RegII is a β-cell protein and autoantigen in diabetes of NOD mice. Diabetes 56:34–40

    Article  PubMed  CAS  Google Scholar 

  • Hartupee JC, Zhang H, Bonaldo MF et al (2001) Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV. Biochim Biophys Acta 1518:287–293

    Article  PubMed  CAS  Google Scholar 

  • Hayashi K, Motoyama S, Koyota S et al (2008a) REG I enhances chemo- and radiosensitivity in squamous cell esophageal cancer cells. Cancer Sci 99:2491–2495

    Article  PubMed  CAS  Google Scholar 

  • Hayashi K, Motoyama S, Sugiyama T et al (2008b) REG Iα is a reliable marker of chemoradiosensitivity in squamous cell esophageal cancer patients. Ann Surg Oncol 15:1224–1231

    Article  PubMed  Google Scholar 

  • Hayashi T, Matsubara A, Ohara S et al (2009) Immunohistochemical analysis of Reg IV in urogenital organs: frequent expression of Reg IV in prostate cancer and potential utility as serum tumor marker. Oncol Rep 21:95–100

    PubMed  Google Scholar 

  • He SQ, Yao JR, Zhang FX et al (2010) Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons. Mol Pain 6:23

    Article  PubMed  CAS  Google Scholar 

  • Heiskala K, Giles-Komar J, Heiskala M, Andersson LC (2006) High expression of RELP (Reg IV) in neoplastic goblet cells of appendiceal mucinous cystadenoma and pseudomyxoma peritonei. Virchows Arch 448:295–300

    Article  PubMed  CAS  Google Scholar 

  • Heiskala K, Arola J, Heiskala M et al (2010) Expression of Reg IV and Hath1 in neuroendocrine neoplasms. Histol Histopathol 25:63–72

    PubMed  CAS  Google Scholar 

  • Heller A, Fiedler F, Schmeck J et al (1999) Pancreatitis-associated protein protects the lung from leukocyte-induced injury. Anesthesiology 91:1408–1414

    Article  PubMed  CAS  Google Scholar 

  • Herve J, Sa Cunha A, Liu B et al (2008) Internal radiotherapy of liver cancer with rat hepatocarcinoma-intestine-pancreas gene as a liver tumor-specific promoter. Hum Gene Ther 19:915–926

    Article  PubMed  CAS  Google Scholar 

  • Hervieu V, Christa L, Gouysse G et al (2006) HIP/PAP, a member of the Reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors. Hum Pathol 37:1066–1075

    Article  PubMed  CAS  Google Scholar 

  • Higham AD, Bishop LA, Dimaline R et al (1999) Mutations of RegIα are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia. Gastroenterology 116:1310–1318

    Article  PubMed  CAS  Google Scholar 

  • Ho MR, Lou YC, Lin WC et al (2006) Human pancreatitis-associated protein forms fibrillar aggregates with a native-like conformation. J Biol Chem 281:33566–33576

    Article  PubMed  CAS  Google Scholar 

  • Ho MR, Lou YC, Wei SY et al (2010) Human RegIV protein adopts a typical C-Type lectin fold but binds mannan with two calcium-independent site\s. J Mol Biol 402:682–695

    Article  PubMed  CAS  Google Scholar 

  • Honda H, Nakamura H, Otsuki M (2002) The elongated PAP-II/Reg-III mRNA is upregulated in rat pancreas during acute experimental pancreatitis. Pancreas 25:192–197

    Article  PubMed  Google Scholar 

  • Huszarik K, Wright B, Keller C et al (2010) Adjuvant immunotherapy increases beta cell regenerative factor Reg-2 in the pancreas of diabetic mice. J Immunol 185:5120–5129

    Article  PubMed  CAS  Google Scholar 

  • Iovanna JL, Dagorn JC (2005) The multifunctional family of secreted proteins containing a C-type lectin-like domain linked to a short N-terminal peptide. Biochim Biophys Acta 1723:8–18

    Article  PubMed  CAS  Google Scholar 

  • Iovanna J, Orelle B, Keim V et al (1991) Messenger RNA sequence and expression of rat pancreatitis-associated protein, a lectin-related protein overexpressed during acute experimental pancreatitis. J Biol Chem 266:24664–24669

    PubMed  CAS  Google Scholar 

  • Iovanna JL, Keim V, Bosshard A et al (1993) PAP, a pancreatic secretory protein induced during acute pancreatitis, is expressed in rat intestine. Am J Physiol 265:G611–G618

    PubMed  CAS  Google Scholar 

  • Iovanna JL, Keim V, Nordback I et al (1994) Serum levels of pancreatitis-associated protein as indicators of the course of acute pancreatitis. Gastroenterology 106:728–734

    PubMed  CAS  Google Scholar 

  • Itoh T, Sawabu N, Motoo Y et al (1995) The human pancreatitis-associated protein (PAP)-encoding gene generates multiple transcripts through alternative use of 5′ exons. Gene 155:283–287

    Article  PubMed  CAS  Google Scholar 

  • Kamimura T, West C, Beutler E (1992) Sequence of a cDNA clone encoding a rat Reg-2 protein. Gene 118:299–300

    Article  PubMed  CAS  Google Scholar 

  • Kandil E, Lin YY, Bluth MH et al (2006) Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins. World J Gastroenterol 12:6806–6811

    PubMed  CAS  Google Scholar 

  • Katsumata N, Chakraborty C, Myal Y et al (1995) Molecular cloning and expression of peptide 23, a growth hormone-releasing hormone-inducible pituitary protein. Endocrinology 136:1332–1339

    Article  PubMed  CAS  Google Scholar 

  • Kazumori H, Ishihara S, Hoshino E et al (2000) Neutrophil chemoattractant 2 β regulates expression of the Reg gene in injured gastric mucosa in rats. Gastroenterology 119:1610–1622

    Article  PubMed  CAS  Google Scholar 

  • Kazumori H, Ishihara S, Fukuda R, Kinoshita Y (2002) Localization of Reg receptor in rat fundic mucosa. J Lab Clin Med 139:101–108

    Article  PubMed  CAS  Google Scholar 

  • Keel M, Härter L, Reding T et al (2009) Pancreatic stone protein is highly increased during posttraumatic sepsis and activates neutrophil granulocytes. Crit Care Med 37:1642–1648

    Article  PubMed  Google Scholar 

  • Keim V, Löffler HG (1986) Pancreatitis-associated protein in bile acid-induced pancreatitis of the rat. Clin Physiol Biochem 4:136–142

    PubMed  CAS  Google Scholar 

  • Keim V, Iovanna JL, Rohr G et al (1991) Characterization of a rat pancreatic secretory protein associated with pancreatitis. Gastroenterology 100:775–782

    PubMed  CAS  Google Scholar 

  • Keim V, Iovanna JL, Orelle B et al (1992) A novel exocrine protein associated with pancreas transplantation in humans. Gastroenterology 103:248–254

    PubMed  CAS  Google Scholar 

  • Keim V, Iovanna JL, Dagorn JC (1994a) The acute phase reaction of the exocrine pancreas. Gene expression and synthesis of pancreatitis-associated proteins. Digestion 55:65–72

    Article  PubMed  CAS  Google Scholar 

  • Keim V, Willemer S, Iovanna JL et al (1994b) Rat pancreatitis-associated protein is expressed in relation to severity of experimental pancreatitis. Pancreas 9:606–612

    Article  PubMed  CAS  Google Scholar 

  • Keim V, Hoffmeister A, Teich N et al (1999) The pancreatitis-associated protein in hereditary and chronic alcoholic pancreatitis. Pancreas 19:248–254

    Article  PubMed  CAS  Google Scholar 

  • Kemppainen E, Sand J, Puolakkainen P et al (1996) Pancreatitis associated protein as an early marker of acute pancreatitis. Gut 39:675–678

    Article  PubMed  CAS  Google Scholar 

  • Kiji T, Dohi Y, Takasawa S et al (2005) Activation of regenerating gene Reg in rat and human hearts in response to acute stress. Am J Physiol Heart Circ Physiol 289:H277–H284

    Article  PubMed  CAS  Google Scholar 

  • Kimura N, Yonekura H, Okamoto H, Nagura H (1992) Expression of human regenerating gene mRNA and its product in normal and neoplastic human pancreas. Cancer 70:1857–1863

    Article  PubMed  CAS  Google Scholar 

  • Kimura T, Fukui H, Sekikawa A et al (2009) Involvement of REG Iα protein in the regeneration of ductal epithelial cells in the minor salivary glands of patients with Sjögren’s syndrome. Clin Exp Immunol 155:16–20

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi S, Akiyama T, Nata K et al (2000) Identification of a receptor for Reg (regenerating gene) protein, a pancreatic β-cell regeneration factor. J Biol Chem 275:10723–10726

    Article  PubMed  CAS  Google Scholar 

  • Kuniyasu H, Oue N, Sasahira T et al (2009) Reg IV enhances peritoneal metastasis in gastric carcinomas. Cell Prolif 42:110–121

    Article  PubMed  CAS  Google Scholar 

  • Lasserre C, Christa L, Simon MT et al (1992) A novel gene (HIP) activated in human primary liver cancer. Cancer Res 52:5089–5095

    PubMed  CAS  Google Scholar 

  • Lasserre C, Simon MT, Ishikawa H et al (1994) Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer. Eur J Biochem 224:29–38

    Article  PubMed  CAS  Google Scholar 

  • Laurine E, Grégoire C, Fändrich M et al (2003) Lithostathine quadruple-helical filaments form proteinase K-resistant deposits in Creutzfeldt-Jakob disease. J Biol Chem 278:51770–51778

    Article  PubMed  CAS  Google Scholar 

  • Laurine E, Manival X, Montgelard C et al (2005) PAP-IB, a new member of the Reg gene family: cloning, expression, structural properties, and evolution by gene duplication. Biochim Biophys Acta 1727:177–187

    Article  PubMed  CAS  Google Scholar 

  • Lechene de la Porte P, de Caro A, Lafont H, Sarles H (1986) Immunocytochemical localization of pancreatic stone protein in the human digestive tract. Pancreas 1:301–308

    Article  PubMed  CAS  Google Scholar 

  • Lee BI, Mustafi D, Cho W, Nakagawa Y (2003) Characterization of calcium binding properties of lithostathine. J Biol Inorg Chem 8:341–347

    PubMed  CAS  Google Scholar 

  • Lehotzky RE, Partch CL, Mukherjee S et al (2010) Molecular basis for peptidoglycan recognition by a bactericidal lectin. Proc Natl Acad Sci USA 107:7722–7727

    Article  PubMed  CAS  Google Scholar 

  • Levine JL, Patel KJ, Zheng Q et al (2000) A recombinant rat regenerating protein is mitogenic to pancreatic derived cells. J Surg Res 89:60–65

    Article  PubMed  CAS  Google Scholar 

  • Li L, Bachem MG, Zhou S et al (2009) Pancreatitis-associated protein inhibits human pancreatic stellate cell MMP-1 and −2, TIMP-1 and −2 secretion and RECK expression. Pancreatology 9:99–110

    Article  PubMed  CAS  Google Scholar 

  • Li B, Wang X, Liu JL (2010a) Pancreatic acinar-specific overexpression of Reg-2 gene offered no protection against either experimental diabetes or pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol 299:G413–G421

    Article  PubMed  CAS  Google Scholar 

  • Li XH, Zheng Y, Zheng HC et al (2010b) REG IV overexpression in an early stage of colorectal carcinogenesis: an immunohistochemical study. Histol Histopathol 25:473–484

    PubMed  Google Scholar 

  • Lieu HT, Batteux F, Simon MT et al (2005) HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice. Hepatology 42:618–626

    Article  PubMed  CAS  Google Scholar 

  • Lieu HT, Simon MT, Nguyen-Khoa T et al (2006) Reg-2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice. Hepatology 44:1452–1464

    Article  PubMed  CAS  Google Scholar 

  • Lim JW, Song JY, Seo JY et al (2009) Role of pancreatitis-associated protein 1 on oxidative stress-induced cell death of pancreatic acinar cells. Ann N Y Acad Sci 1171:545–548

    Article  PubMed  CAS  Google Scholar 

  • Lin YY, Viterbo D, Mueller CM et al (2008) Small-interference RNA gene knockdown of pancreatitis-associated proteins in rat acute pancreatitis. Pancreas 36:402–410

    Article  PubMed  CAS  Google Scholar 

  • Lipsett M, Hanley S, Castellarin M, Austin E, Suarez-Pinzon WL, Rabinovitch A, Rosenberg L (2007) The role of islet neogenesis-associated protein (INGAP) in islet neogenesis. Cell Biochem Biophys 48:127–137

    Article  PubMed  CAS  Google Scholar 

  • Liu JL, Cui W, Li B, Lu Y (2008) Possible roles of Reg family proteins in pancreatic islet cell growth. Endocr Metab Immune Disord Drug Targets 8:1–10

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Liu JL, Srikant CB (2010) Reg-2 protects mouse insulinoma cells from streptozotocin-induced mitochondrial disruption and apoptosis. Growth Factors 28:370–378

    Article  PubMed  CAS  Google Scholar 

  • Livesey FJ, O’Brien JA, Li M et al (1997) A Schwann cell mitogen accompanying regeneration of motor neurons. Nature 390:614–618

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Ponton A, Okamoto H et al (2006) Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas. Am J Physiol Endocrinol Metab 291:E50–E58

    Article  PubMed  CAS  Google Scholar 

  • Mahurkar S, Bhaskar S, Reddy DN et al (2007) Comprehensive screening for Reg 1α gene rules out association with tropical calcific pancreatitis. World J Gastroenterol 13:5938–5943

    PubMed  CAS  Google Scholar 

  • Makino T, Kawashima H, Konishi H et al (2010) Elevated urinary levels and urothelial expression of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein in patients with interstitial cystitis. Urology 75:933–937

    Article  PubMed  Google Scholar 

  • Malka D, Vasseur S, Bodeker H et al (2000) Tumor necrosis factor α triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation. Gastroenterology 119:816–828

    Article  PubMed  CAS  Google Scholar 

  • Mann K, Siedler F (1999) The amino acid sequence of ovocleidin 17, a major protein of the avian eggshell calcified layer. Biochem Mol Biol Int 47:997–1007

    PubMed  CAS  Google Scholar 

  • Masciotra L, Lechêne de la Porte P et al (1995) Immunocytochemical localization of pancreatitis-associated protein in human small intestine. Dig Dis Sci 40:519–524

    Article  PubMed  CAS  Google Scholar 

  • Mauro V, Carette D, Chevallier D et al (2008) Reg I protein in healthy and seminoma human testis. Histol Histopathol 23:1195–1203

    PubMed  CAS  Google Scholar 

  • McCarthy AN, Mogilner IG, Grigera JR et al (2009) Islet neogenesis associated protein (INGAP): structural and dynamical properties of its active pentadecapeptide. J Mol Graph Model 27:701–705

    Article  PubMed  CAS  Google Scholar 

  • McKie AT, Simpson RJ, Ghosh S, Peters TJ, Farzaneh F (1996) Regulation of pancreatitis-associated protein (HIP/PAP) mRNA levels in mouse pancreas and small intestine. Clin Sci 91:213–218

    PubMed  CAS  Google Scholar 

  • Medveczky P, Szmola R, Sahin-Tóth M (2009) Proteolytic activation of human pancreatitis associated protein is required for peptidoglycan binding and bacterial aggregation. Biochem J 420:335–343

    Article  PubMed  CAS  Google Scholar 

  • Minamiya Y, Kawai H, Saito H et al (2008) REG 1A expression is an independent factor predictive of poor prognosis in patients with non-small cell lung cancer. Lung Cancer 60:98–104

    Article  PubMed  Google Scholar 

  • Mitani Y, Oue N, Matsumura S et al (2007) Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy. Oncogene 26:4383–4393

    Article  PubMed  CAS  Google Scholar 

  • Miyaoka Y, Kadowaki Y, Ishihara S et al (2004) Transgenic overexpression of Reg protein caused gastric cell proliferation and differentiation along parietal cell and chief cell lineages. Oncogene 23:3572–3579

    Article  PubMed  CAS  Google Scholar 

  • Miyashita H, Nakagawara K, Mori M et al (1995) Human REG family genes are tandemly ordered in a 95-kilobase region of chromosome 2p12. FEBS Lett 377:429–433

    Article  PubMed  CAS  Google Scholar 

  • Montalto G, Iovanna JL, Soresi M et al (1998) Clinical evaluation of pancreatitis-associated protein as a serum marker of hepatocellular carcinoma: comparison with α-fetoprotein. Oncology 55:421–425

    Article  PubMed  CAS  Google Scholar 

  • Moriizumi S, Watanabe T, Unno M et al (1994) Isolation, structural determination and expression of a novel Reg gene, human RegI β. Biochim Biophys Acta 1217:199–202

    Article  PubMed  CAS  Google Scholar 

  • Moriscot C, Renaud W, Bouvier R et al (1996) Absence of correlation between Reg and insulin gene expression in pancreas during fetal development. Pediatr Res 39:349–353

    Article  PubMed  CAS  Google Scholar 

  • Morisset J, Iovanna J, Grondin G (1997) Localization of rat pancreatitis-associated protein during bile salt-induced pancreatitis. Gastroenterology 112:543–550

    Article  PubMed  CAS  Google Scholar 

  • Motoo Y, Itoh T, Su SB et al (1998) Expression of pancreatitis-associated protein (PAP) mRNA in gastrointestinal cancers. Int J Pancreatol 23:11–16

    PubMed  CAS  Google Scholar 

  • Motoo Y, Satomura Y, Mouri I et al (1999) Serum levels of pancreatitis-associated protein in digestive diseases with special reference to gastrointestinal cancers. Dig Dis Sci 44:1142–1147

    Article  PubMed  CAS  Google Scholar 

  • Motoo Y, Taga K, Su SB et al (2000) Arginine induces apoptosis and gene expression of pancreatitis-associated protein (PAP) in rat pancreatic acinar AR4-2J cells. Pancreas 20:61–66

    Article  PubMed  CAS  Google Scholar 

  • Motoo Y, Watanabe H, Yamaguchi Y et al (2001) Pancreatitis-associated protein levels in pancreatic juice from patients with pancreatic diseases. Pancreatology 1:43–47

    Article  PubMed  CAS  Google Scholar 

  • Motoyama S, Sugiyama T, Ueno Y et al (2006) REG I expression predicts long-term survival among locally advanced thoracic squamous cell esophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. Ann Surg Oncol 13:1724–1731

    Article  PubMed  Google Scholar 

  • Moucadel V, Soubeyran P, Vasseur S et al (2001) Cdx1 promotes cellular growth of epithelial intestinal cells through induction of the secretory protein PAP-I. Eur J Cell Biol 80:156–163

    Article  PubMed  CAS  Google Scholar 

  • Mueller CM, Zhang H, Zenilman ME (2008) Pancreatic Reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells. J Surg Res 150:137–143

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S, Partch CL, Lehotzky RE et al (2009) Regulation of C-type lectin antimicrobial activity by a flexible N-terminal prosegment. J Biol Chem 284:4881–4888

    Article  PubMed  CAS  Google Scholar 

  • Multigner L, Sarles H, Lombardo D, De Caro A (1985) Pancreatic stone protein. II. Implication in stone formation during the course of chronic calcifying pancreatitis. Gastroenterology 89:387–391

    PubMed  CAS  Google Scholar 

  • Namikawa K, Fukushima M, Murakami K et al (2005) Expression of Reg/PAP family members during motor nerve regeneration in rat. Biochem Biophys Res Commun 332:126–134

    Article  PubMed  CAS  Google Scholar 

  • Namikawa K, Okamoto T, Suzuki A et al (2006) Pancreatitis-associated protein-III is a novel macrophage chemoattractant implicated in nerve regeneration. J Neurosci 26:7460–7467

    Article  PubMed  CAS  Google Scholar 

  • Nanakin A, Fukui H, Fujii S et al (2007) Expression of the REG IV gene in ulcerative colitis. Lab Invest 87:304–314

    Article  PubMed  CAS  Google Scholar 

  • Narushima Y, Unno M, Nakagawara K et al (1997) Structure, chromosomal localization and expression of mouse genes encoding type III Reg, Reg-III α, Reg-III β, Reg-III γ. Gene 185:159–168

    Article  PubMed  CAS  Google Scholar 

  • Nata K, Liu Y, Xu L et al (2004) Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG-III. Gene 340:161–170

    Article  PubMed  CAS  Google Scholar 

  • Ng NFL, Hew CL (1992) Structure of an antifreeze polypeptide from the sea raven. J Biol Chem 267:16069–16075

    PubMed  CAS  Google Scholar 

  • Nishimune H, Vasseur S, Wiese S et al (2000) Reg-2 is a motoneuron neurotrophic factor and a signaling intermediate in the CNTF survival pathway. Nat Cell Biol 2:906–914

    Article  PubMed  CAS  Google Scholar 

  • Nordback I, Jaakkola M, Iovanna JL, Dagorn JC (1995) Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking? Gut 36:117–120

    Article  PubMed  CAS  Google Scholar 

  • Norkina O, Graf R, Appenzeller P, De Lisle RC (2006) Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes. BMC Gastroenterol 6:16

    Article  PubMed  CAS  Google Scholar 

  • Ochiai K, Kaneko K, Kitagawa M et al (2004) Activated pancreatic enzyme and pancreatic stone protein (PSP/Reg) in bile of patients with pancreaticobiliary maljunction/choledochal cysts. Dig Dis 49:1953–1956

    Article  Google Scholar 

  • Ogawa H, Fukushima K, Naito H et al (2003) Increased expression of HIP/PAP and regenerating gene III in human inflammatory bowel disease and a murine bacterial reconstitution model. Inflamm Bowel Dis 9:162–170

    Article  PubMed  Google Scholar 

  • Ohara S, Oue N, Matsubara A et al (2008) Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer. Cancer Sci 99:1570–1577

    Article  PubMed  CAS  Google Scholar 

  • Okamoto H (1999) The Reg gene family and Reg proteins: with special attention to the regeneration of pancreatic β-cells. J Hepatobiliary Pancreat Surg 6:254–262

    Article  PubMed  CAS  Google Scholar 

  • Orelle B, Keim V, Masciotra L, Dagorn JC, Iovanna JL (1992) Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. J Clin Invest 90:2284–2291

    Article  PubMed  CAS  Google Scholar 

  • Ortiz EM, Dusetti NJ, Dagorn JC, Iovanna JL (1997) Characterization of a silencer regulatory element in the rat PAP-I gene which confers tissue-specific expression and is promoter-dependent. Arch Biochem Biophys 340:111–116

    Article  PubMed  CAS  Google Scholar 

  • Ortiz EM, Dusetti NJ, Vasseur S et al (1998) The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis. Gastroenterology 114:808–816

    Article  PubMed  CAS  Google Scholar 

  • Ose T, Kadowaki Y, Fukuhara H et al (2007) Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine. Oncogene 26:349–359

    Article  PubMed  CAS  Google Scholar 

  • Oue N, Mitani Y, Aung PP et al (2005) Expression and localization of Reg IV in human neoplastic and non-neoplastic tissues: Reg IV expression is associated with intestinal and neuroendocrine differentiation in gastric adenocarcinoma. J Pathol 207:185–198

    Article  PubMed  CAS  Google Scholar 

  • Oue N, Kuniyasu H, Noguchi T et al (2007) Serum concentration of Reg IV in patients with colorectal cancer: overexpression and high serum levels of Reg IV are associated with liver metastasis. Oncology 72:371–380

    Article  PubMed  CAS  Google Scholar 

  • Oue N, Sentani K, Noguchi T et al (2008) Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma. Am J Surg Pathol 32:1182–1189

    Article  PubMed  Google Scholar 

  • Ozturk M, de la Monte SM, Gross J, Wands JR (1989) Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. Proc Natl Acad Sci USA 86:419–423

    Article  PubMed  CAS  Google Scholar 

  • Patard L, Stoven V, Gharib B et al (1996) What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy. Protein Eng 9:949–957

    Article  PubMed  CAS  Google Scholar 

  • Perfetti R, Hawkins AL et al (1994) Assignment of the human pancreatic regenerating (REG) gene to chromosome 2p12. Genomics 20:305–307

    Article  PubMed  CAS  Google Scholar 

  • Perfetti R, Raygada M et al (1996) Regenerating (Reg) and insulin genes are expressed in prepancreatic mouse embryos. J Mol Endocrinol 17:79–88

    Article  PubMed  CAS  Google Scholar 

  • Petersen TE (1988) The amino-terminal domain of thrombomodulin and pancreatic stone protein are homologous with lectins. FEBS Lett 231:51–53

    Article  PubMed  CAS  Google Scholar 

  • Petersen BE, Zajac VF, Michalopoulos GK (1998) Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 27:1030–1038

    Article  PubMed  CAS  Google Scholar 

  • Pezzilli R, Billi P, Migliori M, Gullo L (1997) Clinical value of pancreatitis-associated protein in acute pancreatitis. Am J Gastroenterol 92:1887–1890

    PubMed  CAS  Google Scholar 

  • Pignol D, Bertrand JA, Bernard JP et al (1995) Crystallization and preliminary crystallographic study of human lithostathine. Proteins 23:604–606

    Article  PubMed  CAS  Google Scholar 

  • Pittenger GL, Taylor-Fishwick DA et al (2007) Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs. Pancreas 34:103–111

    Article  PubMed  Google Scholar 

  • Planas R, Alba A, Carrillo J et al (2006) Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNβ. Diabetologia 49:2379–2387

    Article  PubMed  CAS  Google Scholar 

  • Rafaeloff R, Pittenger GL, Barlow SW et al (1997) Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters. J Clin Invest 99:2100–2109

    Article  PubMed  CAS  Google Scholar 

  • Rechreche H, Montalto G, Mallo GV et al (1999) PAP, Reg Iα and Reg Iβ mRNAs are concomitantly up-regulated during human colorectal carcinogenesis. Int J Cancer 81:688–694

    Article  PubMed  CAS  Google Scholar 

  • Renugopalakrishnan V, Dobbs JC, Collette TW et al (1999) Human pancreatic thread protein, an exocrine thread protein with possible implications to Alzheimer’s disease: secondary structure in solution at acid pH. Biochem Biophys Res Commun 258:653–656

    Article  PubMed  CAS  Google Scholar 

  • Rosty C, Christa L, Kuzdzal S et al (2002) Identification of hepatocarcinoma-intestine pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology. Cancer Res 62:1868–1875

    PubMed  CAS  Google Scholar 

  • Rouimi P, Bonicel J, Rovery M, De Caro A (1987) Cleavage of the Arg-Ile bond in the native polypeptide chain of human pancreatic stone protein. FEBS Lett 216:195–199

    Article  PubMed  CAS  Google Scholar 

  • Rouquier S, Verdier JM, Iovanna J et al (1991) Rat pancreatic stone protein messenger RNA. Abundant expression in mature exocrine cells, regulation by food content, and sequence identity with the endocrine Reg transcript. J Biol Chem 266:786–791

    PubMed  CAS  Google Scholar 

  • Sanchez D, Baeza N, Blouin R et al (2000) Over-expression of the Reg gene in non-obese diabetic mouse pancreas during active diabetogenesis is restricted to exocrine tissue. J Histochem Cytochem 48:1401–1410

    Article  PubMed  CAS  Google Scholar 

  • Sanchez D, Figarella C, Marchand-Pinatel S et al (2001) Preferential expression of Reg Iβ gene in human adult pancreas. Biochem Biophys Res Commun 284:729–737

    Article  PubMed  CAS  Google Scholar 

  • Sanchez D, Gmyr V, Kerr-Conte J et al (2004) Implication of Reg I in human pancreatic duct-like cells in vivo in the pathological pancreas and in vitro during exocrine dedifferentiation. Pancreas 29:14–21

    Article  PubMed  CAS  Google Scholar 

  • Sanchez D, Mueller CM, Zenilman ME (2009) Pancreatic regenerating gene I and acinar cell differentiation: influence on cellular lineage. Pancreas 38:572–577

    Article  PubMed  CAS  Google Scholar 

  • Sansonetti A, Romeo H, Berthezene P et al (1995) Developmental, nutritional, and hormonal regulation of the pancreatitis-associated protein I and III gene expression in the rat small intestine. Scand J Gastroenterol 30:664–669

    Article  PubMed  CAS  Google Scholar 

  • Sarles H, Dagorn JC, Giorgi D, Bernard JP (1990) Renaming pancreatic stone protein as ‘lithostathine’. Gastroenterology 99:900–901

    PubMed  CAS  Google Scholar 

  • Sarles J, Barthellemy S, Férec C et al (1999) Blood concentrations of pancreatitis associated protein in neonates: relevance to neonatal screening for cystic fibrosis. Arch Dis Child Fetal Neonatal Ed 80:F118–F122

    Article  PubMed  CAS  Google Scholar 

  • Sasahara K, Yamaoka T, Moritani M et al (2000) Molecular cloning and tissue-specific expression of a new member of the regenerating protein family, islet neogenesis-associated protein-related protein. Biochim Biophys Acta 1500:142–146

    Article  PubMed  CAS  Google Scholar 

  • Sasahira T, Oue N, Kirita T et al (2008) Reg IV expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland. Histopathology 53:667–675

    Article  PubMed  CAS  Google Scholar 

  • Sasaki Y, Minamiya Y, Takahashi N et al (2008) REG 1A expression is an independent factor predictive of poor prognosis in patients with breast cancer. Ann Surg Oncol 15:3244–3251

    Article  PubMed  Google Scholar 

  • Satomura Y, Sawabu N, Mouri I et al (1995) Measurement of serum PSP/Reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay. J Gastroenterol 30:643–650

    Article  PubMed  CAS  Google Scholar 

  • Schiesser M, Bimmler D, Frick TW, Graf R (2001) Conformational changes of pancreatitis-associated protein (PAP) activated by trypsin lead to insoluble protein aggregates. Pancreas 22:186–192

    Article  PubMed  CAS  Google Scholar 

  • Schmiegel W, Burchert M, Kalthoff H et al (1990) Immunochemical characterization and quantitative distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders. Gastroenterology 99:1421–1430

    PubMed  CAS  Google Scholar 

  • Sekikawa A, Fukui H, Fujii S et al (2005) REG Iα protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer. Gastroenterology 128:642–653

    Article  PubMed  CAS  Google Scholar 

  • Sekikawa A, Fukui H, Fujii S et al (2008) REG Iα protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells. Carcinogenesis 29:76–83

    Article  PubMed  CAS  Google Scholar 

  • Sekikawa A, Fukui H, Suzuki K et al (2010) Involvement of the IL-22/REG Iα axis in ulcerative colitis. Lab Invest 90:496–505

    Article  PubMed  CAS  Google Scholar 

  • Shervani NJ, Takasawa S, Uchigata Y et al (2004) Autoantibodies to REG, a β-cell regeneration factor, in diabetic patients. Eur J Clin Invest 34:752–758

    Article  PubMed  CAS  Google Scholar 

  • Shin JS, Lee JJ, Lee EJ et al (2005) Proteome analysis of rat pancreas induced by pancreatectomy. Biochim Biophys Acta 1749:23–32

    Article  PubMed  CAS  Google Scholar 

  • Simon MT, Pauloin A, Normand G et al (2003) HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. FASEB J 17:1441–1450

    Article  PubMed  CAS  Google Scholar 

  • Skretting G, Austbø L, Olsaker I, Espenes A (2006) Cloning and expression analysis of an ovine PAP-like protein cDNA, a gene differentially expressed in scrapie. Gene 376:116–122

    Article  PubMed  CAS  Google Scholar 

  • Starcević-Klasan G, Azman J, Picard A et al (2008) Reg IV protein is expressed in normal rat tissue. Coll Antropol 32(2):89–93

    PubMed  Google Scholar 

  • Steele IA, Dimaline R, Pritchard DM et al (2007) Helicobacter and gastrin stimulate Reg 1 expression in gastric epithelial cells through distinct promoter elements. Am J Physiol Gastrointest Liver Physiol 293:G347–G354

    Article  PubMed  CAS  Google Scholar 

  • Stephanova E, Tissir F, Dusetti N et al (1996) The rat genes encoding the pancreatitis-associated proteins I, II and III (PAP-I, Pap2, Pap3), and the lithostathin/pancreatic stone protein/regeneration protein (Reg) colocalize at 4q33– > q34. Cytogenet Cell Genet 72:83–85

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Yonekura H, Watanabe T et al (1994) Structure and expression of a novel rat Reg-III gene. Gene 144:315–316

    Article  PubMed  CAS  Google Scholar 

  • Szasz T, Eddy S, Paulauskis J et al (2009) Differential expression of pancreatitis-associated protein and thrombospondins in arterial versus venous tissues. J Vasc Res 46:551–560

    Article  PubMed  CAS  Google Scholar 

  • Takahara Y, Suzuki A, Maeda M et al (2008) Expression of pancreatitis associated proteins in urothelium and urinary afferent neurons following cyclophosphamide induced cystitis. J Urol 179:1603–1609

    Article  PubMed  CAS  Google Scholar 

  • Tam J, Rosenberg L, Maysinger D (2002) Islet-neogenesis-associated protein enhances neurite outgrowth from DRG neurons. Biochem Biophys Res Commun 291:649–654

    Article  PubMed  CAS  Google Scholar 

  • Tam J, Rosenberg L, Maysinger D (2004) INGAP peptide improves nerve function and enhances regeneration in streptozotocin-induced diabetic C57BL/6 mice. FASEB J 18:1767–1769

    PubMed  CAS  Google Scholar 

  • Tamura H, Ohtsuka M, Washiro M et al (2009) Reg IV expression and clinicopathologic features of gallbladder carcinoma. Hum Pathol 40:1686–1692

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Fishwick DA, Rittman S, Kendall H, et al (2003) Cloning genomic INGAP: a Reg-related family member with distinct transcriptional regulation sites. Biochim Biophys Acta 1638:83–89

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Fishwick DA, Shi W, Pittenger GL et al (2006) PDX-1 can repress stimulus-induced activation of the INGAP promoter. J Endocrinol 188:611–621

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Fishwick DA, Bowman A, Korngiebel-Rosique M et al (2008) Pancreatic islet immunoreactivity to the Reg protein INGAP. J Histochem Cytochem 56:183–191

    Article  PubMed  CAS  Google Scholar 

  • Tebar LA, Géranton SM, Parsons-Perez C et al (2008) Deletion of the mouse Reg-IIIβ (Reg-2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons. Natl Acad Sci USA 105:11400–11405

    Article  CAS  Google Scholar 

  • Terazono K, Yamamoto H, Takasawa S et al (1988) A novel gene activated in regenerating islets. J Biol Chem 263:2111–2114

    PubMed  CAS  Google Scholar 

  • Terazono K, Uchiyama Y, Ide M et al (1990) Expression of reg protein in rat regenerating islets and its co-localization with insulin in the β cell secretory granules. Diabetologia 33:250–252

    Article  PubMed  CAS  Google Scholar 

  • Unno M, Yonekura H, Nakagawara K et al (1993) Structure, chromosomal localization, and expression of mouse Reg genes, Reg I and Reg II. A novel type of Reg gene, Reg II, exists in the mouse genome. J Biol Chem 268:15974–15982

    PubMed  CAS  Google Scholar 

  • Usami S, Motoyama S, Koyota S et al (2010) Regenerating gene I regulates interleukin-6 production in squamous esophageal cancer cells. Biochem Biophys Res Commun 392:4–8

    Article  PubMed  CAS  Google Scholar 

  • Valery C, Vasseur S, Sabatier F et al (2001) Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human melanocytes and melanoma cells. J Invest Dermatol 116:426–433

    Article  PubMed  CAS  Google Scholar 

  • van Ampting MT, Rodenburg W, Vink C et al (2009) Ileal mucosal and fecal pancreatitis associated protein levels reflect severity of Salmonella infection in rats. Dig Dis Sci 54:2588–2597

    Article  PubMed  CAS  Google Scholar 

  • van der Pijl JW, Boonstra JG et al (1997) Pancreatitis-associated protein: a putative marker for pancreas graft rejection. Transplantation 63:995–1003

    Article  PubMed  Google Scholar 

  • Vasseur S, Frigerio JM, Dusetti NJ et al (1995) Two transcripts are generated from the pancreatitis associated protein II gene by alternative splicing in the 5′ untranslated region. Biochim Biophys Acta 1261:272–274

    Article  PubMed  Google Scholar 

  • Vasseur S, Folch-Puy E, Hlouschek V, Iovanna JL et al (2004) p8 improves pancreatic response to acute pancreatitis by enhancing the expression of the anti-inflammatory protein pancreatitis-associated protein I. J Bio Chem 279:7199–7207

    Article  CAS  Google Scholar 

  • Violette S, Festor E, Pandrea-Vasile I et al (2003) Reg IV, a new member of the Regenerating gene family, is overexpressed in colorectal carcinomas. Int J Cancer 103:185–193

    Article  PubMed  CAS  Google Scholar 

  • Viterbo D, Bluth MH, Lin YY et al (2008a) Pancreatitis-associated protein 2 modulates inflammatory responses in macrophages. J Immunol 181:1948–1958

    PubMed  CAS  Google Scholar 

  • Viterbo D, Bluth MH, Mueller CM et al (2008b) Mutational characterization of pancreatitis-associated protein 2 domains involved in mediating cytokine secretion in macrophages and the NF-kB pathway. J Immunol 181:1959–1968

    PubMed  CAS  Google Scholar 

  • Viterbo D, Callender GE, DiMaio T et al (2009) Administration of anti-Reg I and anti-PAP-II antibodies worsens pancreatitis. JOP 10:15–23

    PubMed  Google Scholar 

  • Walker LC, LeVineH III (2000) The cerebral proteopathies. Neurobiol Aging 21:559–561

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Wang B, Wu J (2001) Pancreatitis-associated protein-I mRNA expression in mouse pancreas is upregulated by lipopolysaccharide independent of cerulein-pancreatitis. J Gastroenterol Hepatol 16:79–86

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Koyota S, Zhou X et al (2009) Expression and localization of regenerating gene I in a rat liver regeneration model. Biochem Biophys Res Commun 380:472–477

    Article  PubMed  CAS  Google Scholar 

  • Watanabe T, Yonekura H, Terazono K et al (1990) Complete nucleotide sequence of human Reg gene and its expression in normal and tumoral tissues. The Reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene. J Biol Chem 265:7432–7439

    PubMed  CAS  Google Scholar 

  • Watanabe T, Yonemura Y, Yonekura H et al (1994) Pancreatic β-cell replication and amelioration of surgical diabetes by Reg protein. Proc Natl Acad Sci USA 91:3589–3592

    Article  PubMed  CAS  Google Scholar 

  • Watanabe R, Hanawa H, Yoshida T et al (2008) Gene expression profiles of cardiomyocytes in rat autoimmune myocarditis by DNA microarray and increase of regenerating gene family. Transl Res 152:119–127

    Article  PubMed  CAS  Google Scholar 

  • Wittel UA, Pandey KK, Andrianifahanana M et al (2006) Chronic pancreatic inflammation induced by environmental tobacco smoke inhalation in rats. Am J Gastroenterol 101:148–159

    Article  PubMed  CAS  Google Scholar 

  • Xie MJ, Motoo Y, Iovanna JL et al (2003) Overexpression of pancreatitis-associated protein (PAP) in human pancreatic ductal adenocarcinoma. Dig Dis Sci 48:459–464

    Article  PubMed  CAS  Google Scholar 

  • Xu YY, Wands JR, de la Monte SM (1993) Characterization of thread proteins expressed in neuroectodermal tumors. Cancer Res 53:3823–3829

    PubMed  CAS  Google Scholar 

  • Xu YY, Bhavani K, Wands JR et al (1995a) Ethanol inhibits insulin receptor substrate-1 tyrosine phosphorylation and insulin-stimulated neuronal thread protein gene expression. Biochem J 310:125–132

    PubMed  CAS  Google Scholar 

  • Xu YY, Bhavani K, Wands JR et al (1995b) Insulin-induced differentiation and modulation of neuronal thread protein expression in primitive neuroectodermal tumor cells is linked to phosphorylation of insulin receptor substrate-1. J Mol Neurosci 6:91–108

    Article  PubMed  CAS  Google Scholar 

  • Yamagishi H, Fukui H, Sekikawa A et al (2009) Expression profile of REG family proteins REG Iα and REG IV in advanced gastric cancer: comparison with mucin phenotype and prognostic markers. Mod Pathol 22:906–913

    Article  PubMed  CAS  Google Scholar 

  • Yamauchi A, Takahashi I, Takasawa S et al (2009) Thiazolidinediones inhibit REG Iα gene transcription in gastrointestinal cancer cells. Biochem Biophys Res Commun 379:743–748

    Article  PubMed  CAS  Google Scholar 

  • Yasui W, Oue N, Sentani K et al (2009) Transcriptome dissection of gastric cancer: identification of novel diagnostic and therapeutic targets from pathology specimens. Pathol Int 59:121–136

    Article  PubMed  CAS  Google Scholar 

  • Yonemura Y, Sakurai S et al (2003) REG gene expression is associated with the infiltrating growth of gastric carcinoma. Cancer 98:1394–1400

    Article  PubMed  CAS  Google Scholar 

  • Yoshida K, Yasui W (2009) Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients. Int J Cancer 125:2383–2392

    Article  PubMed  CAS  Google Scholar 

  • Yoshino N, Ishihara S, Rumi MA et al (2005) Interleukin-8 regulates expression of Reg protein in Helicobacter pylori-infected gastric mucosa. Am J Gastroenterol 100:2157–2166

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka S, Fujii S, Richards JS, Espey LL (2002) Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in the rat ovary at the time of ovulation. J Endocrinol 174:485–492

    Article  PubMed  CAS  Google Scholar 

  • Yuan RH, Jeng YM, Chen HL et al (2005) Opposite roles of human pancreatitis-associated protein and REG 1A expression in hepatocellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, β-catenin mutation, and favorable prognosis. Clin Cancer Res 11:2568–2575

    Article  PubMed  CAS  Google Scholar 

  • Zenilman ME, Magnuson TH et al (1996) Pancreatic thread protein is mitogenic to pancreatic-derived cells in culture. Gastroenterology 110:1208–1214

    Article  PubMed  CAS  Google Scholar 

  • Zenilman ME, Kim S, Levine BA et al (1997) Ectopic expression of Reg protein: a marker of colorectal mucosa at risk for neoplasia. J Gastrointest Surg 1:194–201

    Article  PubMed  CAS  Google Scholar 

  • Zenilman ME, Chen J, Magnuson TH (1998) Effect of Reg protein on rat pancreatic ductal cells. Pancreas 17:256–261

    Article  PubMed  CAS  Google Scholar 

  • Zenilman ME, Tuchman D, Zheng Q et al (2000) Comparison of Reg I and Reg-III levels during acute pancreatitis in the rat. Ann Surg 232:646–652

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Realini C, Clawson A et al (1998) Proteasome activation by REG molecules lacking homolog-specific inserts. J Biol Chem 273:9501–9509

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Lai M, Lv B et al (2003a) Overexpression of Reg IV in colorectal adenoma. Cancer Lett 200:69–76

    Article  PubMed  CAS  Google Scholar 

  • Zhang YW, Ding LS, Lai MD (2003b) Reg gene family and human diseases. World J Gastroenterol 9:2635–2641

    PubMed  CAS  Google Scholar 

  • Zhang H, Kandil E, Lin YY et al (2004) Targeted inhibition of gene expression of pancreatitis-associated proteins exacerbates the severity of acute pancreatitis in rats. Scand J Gastroenterol 39:870–881

    Article  PubMed  CAS  Google Scholar 

  • Zheng HC, Xu XY, Yu M et al (2010) The role of Reg IV gene and its encoding product in gastric carcinogenesis. Hum Pathol 41:59–69

    Article  PubMed  CAS  Google Scholar 

  • Zhong B, Pavel Strnad P, Diana M, Toivola DM et al (2007) Reg-II is an exocrine pancreas injury-response product that is up-regulated by keratin absence or mutation. Mol Biol Cell 18:4969–4978

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biophysics, Punjab University, Chandigarh, India

    G. S. Gupta (Former Professor and Chairman)

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Gupta, G.S. (2012). Regenerating (Reg) Gene Family. In: Animal Lectins: Form, Function and Clinical Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1065-2_39

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