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Cellular Effects of Progranulin in Health and Disease

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Abstract

Progranulin is a fascinating multifunctional protein, which has been implicated in cell growth, wound repair, tumorigenesis, inflammation, neurodevelopment, and more recently in neurodegeneration. The mechanism of action of this protein is still largely unknown, but the knowledge about the cellular effects on various cell types is expanding. In the current review, we will summarize what is known about the cell biology of progranulin. A better understanding of the biology of progranulin will impact diverse areas of research.

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References

  • Ahmed Z, Sheng H, Xu Y-F et al (2010) Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am J Pathol 177:311–324

    Article  PubMed  CAS  Google Scholar 

  • Anakwe OO, Gerton GL (1990) Acrosome biogenesis begins during meiosis: evidence from the synthesis and distribution of an acrosomal glycoprotein, acrogranin, during guinea pig spermatogenesis. Biol Reprod 42:317–328

    Article  PubMed  CAS  Google Scholar 

  • Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611

    Article  PubMed  CAS  Google Scholar 

  • Ashcroft GS, Lei K, Jin W et al (2000) Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med 6:1147–1153

    Article  PubMed  CAS  Google Scholar 

  • Bai X-H, Wang D-W, Kong L et al (2009) ADAMTS-7, a direct target of PTHrP, adversely regulates endochondral bone growth by associating with and inactivating GEP growth factor. Mol Cell Biol 29:4201–4219

    Article  PubMed  CAS  Google Scholar 

  • Baker CA, Manuelidis L (2003) Unique inflammatory RNA profiles of microglia in Creutzfeldt–Jakob disease. Proc Natl Acad Sci 100:675–679

    Article  PubMed  CAS  Google Scholar 

  • Baker M, Mackenzie IR, Pickering-Brown SM et al (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442:916–919

    Article  PubMed  CAS  Google Scholar 

  • Baladrón V, Ruiz-Hidalgo MJ, Bonvini E, Gubina E, Notario V, Laborda J (2002) The EGF-like homeotic protein dlk affects cell growth and interacts with growth-modulating molecules in the yeast two-hybrid system. Biochem Biophys Res Commun 291:193–204

    Article  PubMed  CAS  Google Scholar 

  • Benarafa C, Priebe GP, Remold-O’Donnell E (2007) The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection. J Exp Med 204:1901–1909

    Article  PubMed  CAS  Google Scholar 

  • Bhandari V, Bateman A (1992) Structure and chromosomal location of the human granulin gene. Biochem Biophys Res Commun 188:57–63

    Article  PubMed  CAS  Google Scholar 

  • Bhandari V, Palfree RG, Bateman A (1992) Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Proc Natl Acad Sci 89:1715–1719

    Article  PubMed  CAS  Google Scholar 

  • Butler GS, Dean RA, Tam EM, Overall CM (2008) Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding. Mol Cell Biol 28:4896–4914

    Article  PubMed  CAS  Google Scholar 

  • Cao Z, Jiang B, Xie Y, Liu C-J, Feng JQ (2010) GEP, a local growth factor, is critical for odontogenesis and amelogenesis. Int J Biol Sci 6:719–729

    PubMed  CAS  Google Scholar 

  • Carrasquillo MM, Nicholson AM, Finch N et al (2010) Genome-wide screen identifies rs646776 near sortilin as a regulator of progranulin levels in human plasma. Am J Hum Genet 87:890–897

    Article  PubMed  CAS  Google Scholar 

  • Chen X-Y, Li J-S, Liang Q-P, He D-Z, Zhao J (2008) Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J 121:881–886

    PubMed  CAS  Google Scholar 

  • Chen-Plotkin AS, Lee VMY, Trojanowski JQ (2010) TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 6:211–220

    Article  PubMed  CAS  Google Scholar 

  • Cheung ST, Wong SY, Leung KL et al (2004) Granulin–epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma. Clin Cancer Res 10:7629–7636

    Article  PubMed  CAS  Google Scholar 

  • Cheung ST, Wong SY, Lee YT, Fan ST (2006) GEP associates with wild-type p53 in hepatocellular carcinoma. Oncol Rep 15:1507–1511

    PubMed  CAS  Google Scholar 

  • Cheung ST, Cheung PFY, Cheng CKC, Wong NCL, Fan ST (2011) Granulin–epithelin precursor and ATP-dependent binding cassette (ABC)B5 regulate liver cancer cell chemoresistance. Gastroenterology 140:344–355

    Article  PubMed  CAS  Google Scholar 

  • Chitramuthu BP, Baranowski DC, Kay DG, Bateman A, Bennett HP (2010) Progranulin modulates zebrafish motoneuron development in vivo and rescues truncation defects associated with knockdown of survival motor neuron 1. Mol Neurodegener 5:41

    Article  PubMed  CAS  Google Scholar 

  • Coppola G, Karyda A, Rademakers R et al (2008) Gene expression study on peripheral blood identifies progranulin mutations. Ann Neurol 64:92–96

    Article  PubMed  CAS  Google Scholar 

  • Cruchaga C, Fernández-Seara MA, Seijo-Martínez M et al (2009) Cortical atrophy and language network reorganization associated with a novel progranulin mutation. Cereb Cortex 19:1751–1760

    Article  PubMed  Google Scholar 

  • Cruts M, Gijselinck I, van der Zee J et al (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442:920–924

    Article  PubMed  CAS  Google Scholar 

  • Culouscou JM, Carlton GW, Shoyab M (1993) Biochemical analysis of the epithelin receptor. J Biol Chem 268:10458–10462

    PubMed  CAS  Google Scholar 

  • Daniel R, He Z, Carmichael KP, Halper J, Bateman A (2000) Cellular localization of gene expression for progranulin. J Histochem Cytochem 48:999–1009

    Article  PubMed  CAS  Google Scholar 

  • Daniel R, Daniels E, He Z, Bateman A (2003) Progranulin (acrogranin/PC cell-derived growth factor/granulin–epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. Dev Dyn 227:593–599

    Article  PubMed  CAS  Google Scholar 

  • Díaz-Cueto L, Stein P, Jacobs A, Schultz RM, Gerton GL (2000) Modulation of mouse preimplantation embryo development by acrogranin (epithelin/granulin precursor). Dev Biol 217:406–418

    Article  PubMed  CAS  Google Scholar 

  • Dormann D, Capell A, Carlson AM et al (2009) Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin. J Neurochem 110:1082–1094

    Article  PubMed  CAS  Google Scholar 

  • Elkabets M, Gifford AM, Scheel C et al (2011) Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice. J Clin Invest 121:784–799

    Article  PubMed  CAS  Google Scholar 

  • Feng JQ, Guo F-J, Jiang B-C et al (2010) Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. FASEB J 24:1879–1892

    Article  PubMed  CAS  Google Scholar 

  • Finch N, Baker M, Crook R et al (2009) Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 132:583–591

    Article  PubMed  Google Scholar 

  • Gao X, Joselin AP, Wang L et al (2010) Progranulin promotes neurite outgrowth and neuronal differentiation by regulating GSK-3β. Protein Cell 1:552–562

    Article  PubMed  CAS  Google Scholar 

  • Ghidoni R, Benussi L, Glionna M, Franzoni M, Binetti G (2008) Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology 71:1235–1239

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez E, Mongiat M, Slater S, Baffa R, Iozzo R (2003) A novel interaction between perlecan protein core and progranulin—potential effects on tumor growth. J Biol Chem 278:38113–38116

    Article  PubMed  CAS  Google Scholar 

  • Guerra RR, Kriazhev L, Hernandez-Blazquez FJ, Bateman A (2007) Progranulin is a stress-response factor in fibroblasts subjected to hypoxia and acidosis. Growth Factors 25:280–285

    Article  PubMed  CAS  Google Scholar 

  • Guo F, Lai Y, Tian Q, Lin EA, Kong L, Liu C (2010) Granulin–epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein. Arthritis Rheum 62:2023–2036

    PubMed  CAS  Google Scholar 

  • Han JJ, Yu M, Houston N, Steinberg SM, Kohn EC (2011) Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers. Gynecol Oncol 120:5–10

    Article  PubMed  CAS  Google Scholar 

  • He Z, Bateman A (1999) Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res 59:3222–3229

    PubMed  CAS  Google Scholar 

  • He Z, Bateman A (2003) Progranulin (granulin–epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med 81:600–612

    Article  PubMed  CAS  Google Scholar 

  • He Z, Ismail A, Kriazhev L, Sadvakassova G, Bateman A (2002) Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res 62:5590–5596

    PubMed  CAS  Google Scholar 

  • He Z, Ong CHP, Halper J, Bateman A (2003) Progranulin is a mediator of the wound response. Nat Med 9:225–229

    Article  PubMed  CAS  Google Scholar 

  • Ho JC, Ip YC, Cheung ST et al (2008) Granulin–epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology 47:1524–1532

    Article  PubMed  CAS  Google Scholar 

  • Hoque M, Young TM, Lee C-G, Serrero G, Mathews MB, Pe’ery T (2003) The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription. Mol Cell Biol 23:1688–1702

    Article  PubMed  CAS  Google Scholar 

  • Hoque M, Tian B, Mathews MB, Pe’ery T (2005) Granulin and granulin repeats interact with the Tat.P-TEFb complex and inhibit Tat transactivation. J Biol Chem 280:13648–13657

    Article  PubMed  CAS  Google Scholar 

  • Hoque M, Mathews MB, Pe’ery T (2010) Progranulin (granulin/epithelin precursor) and its constituent granulin repeats repress transcription from cellular promoters. J Cell Physiol 223:224–233

    PubMed  CAS  Google Scholar 

  • Hrabal R, Chen Z, James S, Bennett HP, Ni F (1996) The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Nat Struct Biol 3:747–752

    Article  PubMed  CAS  Google Scholar 

  • Hu F, Padukkavidana T, Vægter CB et al (2010) Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin. Neuron 68:654–667

    Article  PubMed  CAS  Google Scholar 

  • Johnston C, Jiang W, Chu T, Levine B (2001) Identification of genes involved in the host response to neurovirulent alphavirus infection. J Virol 75:10431–10445

    Article  PubMed  CAS  Google Scholar 

  • Jones MB, Michener CM, Blanchette JO et al (2003) The granulin–epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer. Clin Cancer Res 9:44–51

    PubMed  CAS  Google Scholar 

  • Kao AW, Eisenhut RJ, Martens LH et al (2011) A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells. Proc Natl Acad Sci 108:4441–4446

    Article  PubMed  CAS  Google Scholar 

  • Kato M, Hasunuma N, Nakayama R et al (2009) Progranulin, a secreted tumorigenesis and dementia-related factor, regulates mouse hair growth. J Dermatol Sci 53:234–236

    Article  PubMed  CAS  Google Scholar 

  • Kessenbrock K, Fröhlich L, Sixt M et al (2008) Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Invest 118:2438–2447

    PubMed  CAS  Google Scholar 

  • Kim WE, Serrero G (2006) PC cell-derived growth factor stimulates proliferation and confers Trastuzumab resistance to Her-2-overexpressing breast cancer cells. Clin Cancer Res 12:4192–4199

    Article  PubMed  CAS  Google Scholar 

  • Kojima Y, Ono K, Inoue K et al (2009) Progranulin expression in advanced human atherosclerotic plaque. Atherosclerosis 206:102–108

    Article  PubMed  CAS  Google Scholar 

  • Laird AS, Van Hoecke A, De Muynck L et al (2010) Progranulin is neurotrophic in vivo and protects against a mutant TDP-43 induced axonopathy. PLoS ONE 5:e13368

    Article  PubMed  CAS  Google Scholar 

  • Li X, Massa PE, Hanidu A et al (2002) IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J Biol Chem 277:45129–45140

    Article  PubMed  CAS  Google Scholar 

  • Li Y-H, Chen MH-C, Gong H-Y et al (2010) Progranulin A-mediated MET signaling is essential for liver morphogenesis in zebrafish. J Biol Chem 285:41001–41009

    Article  PubMed  CAS  Google Scholar 

  • Liau LM, Lallone RL, Seitz RS et al (2000) Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Cancer Res 60:1353–1360

    PubMed  CAS  Google Scholar 

  • Lin W-L, Zehr C, Lewis J, Dickson DW (2007) Progranulin is located in secretory granules and vesicles of neutrophils and macrophages by immunogold electron microscopy: 41.7. J Neuropathol Exp Neurol 66:422

    Article  Google Scholar 

  • Lu R, Serrero G (2000) Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. Proc Natl Acad Sci 97:3993–3998

    Article  PubMed  CAS  Google Scholar 

  • Lu R, Serrero G (2001) Mediation of estrogen mitogenic effect in human breast cancer MCF-7 cells by PC-cell-derived growth factor (PCDGF/granulin precursor). Proc Natl Acad Sci 98:142–147

    Article  PubMed  CAS  Google Scholar 

  • Mackenzie IRA, Baker M, Pickering-Brown S et al (2006) The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene. Brain 129:3081–3090

    Article  PubMed  Google Scholar 

  • Malaspina A, Kaushik N, de Belleroche J (2001) Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays. J Neurochem 77:132–145

    Article  PubMed  CAS  Google Scholar 

  • Matsumura N, Mandai M, Miyanishi M et al (2006) Oncogenic property of acrogranin in human uterine leiomyosarcoma: direct evidence of genetic contribution in in vivo tumorigenesis. Clin Cancer Res 12:1402–1411

    Article  PubMed  CAS  Google Scholar 

  • Matzilevich DA, Rall JM, Moore AN, Grill RJ, Dash PK (2002) High-density microarray analysis of hippocampal gene expression following experimental brain injury. J Neurosci Res 67:646–663

    Article  PubMed  CAS  Google Scholar 

  • Miyanishi M, Mandai M, Matsumura N et al (2007) Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression. Oncol Rep 17:329–333

    PubMed  CAS  Google Scholar 

  • Moisse K, Volkening K, Leystra-Lantz C, Welch I, Hill T, Strong MJ (2009) Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res 1249:202–211

    Article  PubMed  CAS  Google Scholar 

  • Monami G, Gonzalez EM, Hellman M et al (2006) Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex. Cancer Res 66:7103–7110

    Article  PubMed  CAS  Google Scholar 

  • Monami G, Emiliozzi V, Bitto A et al (2009) Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth. Am J Pathol 174:1037–1047

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee O, Wang J, Gitcho MA et al (2008) Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. Hum Mutat 29:512–521

    Article  PubMed  CAS  Google Scholar 

  • Naphade SB, Kigerl KA, Jakeman LB, Kostyk SK, Popovich PG, Kuret J (2010) Progranulin expression is upregulated after spinal contusion in mice. Acta Neuropathol 119:123–133

    Article  PubMed  CAS  Google Scholar 

  • Neary D, Snowden J, Mann D (2005) Frontotemporal dementia. Lancet Neurol 4:771–780

    Article  PubMed  Google Scholar 

  • Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133

    Article  PubMed  CAS  Google Scholar 

  • Ohmi K, Greenberg DS, Rajavel KS, Ryazantsev S, Li HH, Neufeld EF (2003) Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB. Proc Natl Acad Sci 100:1902–1907

    Article  PubMed  CAS  Google Scholar 

  • Okura H, Yamashita S, Ohama T et al (2010) HDL/apolipoprotein A–I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins. J Atheroscler Thromb 17:568–577

    Article  PubMed  CAS  Google Scholar 

  • Petkau TL, Neal SJ, Orban PC et al (2010) Progranulin expression in the developing and adult murine brain. J Comp Neurol 518:3931–3947

    Article  PubMed  Google Scholar 

  • Philips T, Robberecht W (2011) Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol 10:253–263

    Article  PubMed  CAS  Google Scholar 

  • Philips T, De Muynck L, Thu HNT et al (2010) Microglial upregulation of progranulin as a marker of motor neuron degeneration. J Neuropathol Exp Neurol 69:1191–1200

    Article  PubMed  CAS  Google Scholar 

  • Pickford F, Marcus J, Camargo LM et al (2011) Progranulin is a chemoattractant for microglia and stimulates their endocytic activity. Am J Pathol 178:284–295

    Article  PubMed  CAS  Google Scholar 

  • Pizarro GO, Zhou XC, Koch A et al (2007) Prosurvival function of the granulin–epithelin precursor is important in tumor progression and chemoresponse. Int J Cancer 120:2339–2343

    Article  PubMed  CAS  Google Scholar 

  • Plowman GD, Green JM, Neubauer MG et al (1992) The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. J Biol Chem 267:13073–13078

    PubMed  CAS  Google Scholar 

  • Qin J, Díaz-Cueto L, Schwarze J et al (2005) Effects of progranulin on blastocyst hatching and subsequent adhesion and outgrowth in the mouse. Biol Reprod 73:434–442

    Article  PubMed  CAS  Google Scholar 

  • Ratnavalli E, Brayne C, Dawson K, Hodges JR (2002) The prevalence of frontotemporal dementia. Neurology 58:1615–1621

    PubMed  CAS  Google Scholar 

  • Ryan CL, Baranowski DC, Chitramuthu BP et al (2009) Progranulin is expressed within motor neurons and promotes neuronal cell survival. BMC Neurosci 10:130

    Article  PubMed  CAS  Google Scholar 

  • Shankaran SS, Capell A, Hruscha AT et al (2008) Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretion. J Biol Chem 283:1744–1753

    Article  PubMed  CAS  Google Scholar 

  • Shoyab M, McDonald VL, Byles C, Todaro GJ, Plowman GD (1990) Epithelins 1 and 2: isolation and characterization of two cysteine-rich growth-modulating proteins. Proc Natl Acad Sci 87:7912–7916

    Article  PubMed  CAS  Google Scholar 

  • Sleegers K, Brouwers N, Van Damme P et al (2009) Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol 65:603–609

    Article  PubMed  CAS  Google Scholar 

  • Song G, Ouyang G, Bao S (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9:59–71

    Article  PubMed  CAS  Google Scholar 

  • Stubert J, Richter D-U, Gerber B, Briese V (2010) Expression pattern of progranulin in the human placenta and its effect on cell proliferation in the choriocarcinoma cell line BeWo. J Reprod Dev 57:229–235

    Google Scholar 

  • Sui D, Wilson JE (2000) Interaction of insulin-like growth factor binding protein-4, Miz-1, leptin, lipocalin-type prostaglandin D synthase, and granulin precursor with the N-terminal half of type III hexokinase. Arch Biochem Biophys 382:262–274

    Article  PubMed  CAS  Google Scholar 

  • Tang W, Lu Y, Tian Q-Y et al (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332:478–484

    Article  PubMed  CAS  Google Scholar 

  • Tangkeangsirisin W, Serrero G (2004) PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells. Carcinogenesis 25:1587–1592

    Article  PubMed  CAS  Google Scholar 

  • Tangkeangsirisin W, Hayashi J, Serrero G (2004) PC cell-derived growth factor mediates tamoxifen resistance and promotes tumor growth of human breast cancer cells. Cancer Res 64:1737–1743

    Article  PubMed  CAS  Google Scholar 

  • Trinh DP, Brown KM, Jeang KT (1999) Epithelin/granulin growth factors: extracellular cofactors for HIV-1 and HIV-2 Tat proteins. Biochem Biophys Res Commun 256:299–306

    Article  PubMed  CAS  Google Scholar 

  • Uesaka T, Yano K, Yamasaki M, Ando M (1995) Somatostatin-, vasoactive intestinal eptide-, and granulin-like peptides isolated from intestinal extracts of goldfish, Carassius auratus. Gen Comp Endocrinol 99:298–306

    Article  PubMed  CAS  Google Scholar 

  • Van Damme P, Van Hoecke A, Lambrechts D et al (2008) Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 181:37–41

    Article  PubMed  CAS  Google Scholar 

  • van der Zee J, Le Ber I, Maurer-Stroh S et al (2007) Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum Mutat 28:416

    PubMed  Google Scholar 

  • Wang W, Hayashi J, Kim WE, Serrero G (2003) PC cell-derived growth factor (granulin precursor) expression and action in human multiple myeloma. Clin Cancer Res 9:2221–2228

    PubMed  CAS  Google Scholar 

  • Wang W, Hayashi J, Serrero G (2006) PC cell-derived growth factor confers resistance to dexamethasone and promotes tumorigenesis in human multiple myeloma. Clin Cancer Res 12:49–56

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Van Damme P, Cruchaga C et al (2010) Pathogenic cysteine mutations affect progranulin function and production of mature granulins. J Neurochem 112:1305–1315

    Article  PubMed  CAS  Google Scholar 

  • Xia X, Serrero G (1998) Identification of cell surface binding sites for PC-cell-derived growth factor, PCDGF, (epithelin/granulin precursor) on epithelial cells and fibroblasts. Biochem Biophys Res Commun 245:539–543

    Article  PubMed  CAS  Google Scholar 

  • Xu SQ, Tang D, Chamberlain S et al (1998) The granulin/epithelin precursor abrogates the requirement for the insulin-like growth factor 1 receptor for growth in vitro. J Biol Chem 273:20078–20083

    Article  PubMed  CAS  Google Scholar 

  • Xu K, Zhang Y, Ilalov K et al (2007) Cartilage oligomeric matrix protein associates with granulin–epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation. J Biol Chem 282:11347–11355

    Article  PubMed  CAS  Google Scholar 

  • Xu D, Suenaga N, Edelmann MJ, Fridman R, Muschel RJ, Kessler BM (2008) Novel MMP-9 substrates in cancer cells revealed by a label-free quantitative proteomics approach. Mol Cell Proteomics 7:2215–2228

    Article  PubMed  CAS  Google Scholar 

  • Yin F, Banerjee R, Thomas B et al (2010a) Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med 207:117–128

    Article  PubMed  CAS  Google Scholar 

  • Yin F, Dumont M, Banerjee R et al (2010b) Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia. FASEB J 24:4639–4647

    Article  PubMed  CAS  Google Scholar 

  • Youn B-S, Bang S-I, Kloeting N et al (2009) Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes 58:627–636

    Article  PubMed  CAS  Google Scholar 

  • Zanocco-Marani T, Bateman A, Romano G, Valentinis B, He ZH, Baserga R (1999) Biological activities and signaling pathways of the granulin/epithelin precursor. Cancer Res 59:5331–5340

    PubMed  CAS  Google Scholar 

  • Zhang H, Serrero G (1998) Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor). Proc Natl Acad Sci 95:14202–14207

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y-J, Xu Y-F, Dickey CA et al (2007) Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J Neurosci 27:10530–10534

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Gao G, Crabb JW, Serrero G (1993) Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. J Biol Chem 268:10863–10869

    PubMed  CAS  Google Scholar 

  • Zhu J, Nathan C, Jin W et al (2002) Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111:867–878

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

L. D. M. holds a PhD grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen). P. V. D. is supported by the Fund for Scientific Research Flanders (FWO-V) and by the Stichting voor Alzheimer Onderzoek Belgium (SAO-FRMA #08615). P. V. D. holds a clinical investigatorship of the FWO-V.

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  1. Vesalius Research Center, VIB, Leuven, Belgium

    Louis De Muynck & Philip Van Damme

  2. Laboratory of Neurobiology, K.U. Leuven, Leuven, Belgium

    Louis De Muynck & Philip Van Damme

  3. Department of Neurology, K.U. Leuven, Leuven, Belgium

    Philip Van Damme

  4. Department of Neurology, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium

    Philip Van Damme

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  1. Louis De Muynck
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Correspondence to Philip Van Damme.

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De Muynck, L., Van Damme, P. Cellular Effects of Progranulin in Health and Disease. J Mol Neurosci 45, 549–560 (2011). https://doi.org/10.1007/s12031-011-9553-z

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