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Mucosal repair and growth factors: recombinant human hepatocyte growth factor as an innovative therapy for inflammatory bowel disease

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Abstract

The repair of intestinal mucosal injuries is a tightly regulated process involving epithelial restitution, cell proliferation and maturation, and the dedifferentiation of epithelial cells. Deeper injuries also require additional repair mechanisms, including inflammatory processes, angiogenesis, and extracellular-matrix deposition. Once intestinal mucosal injury occurs, numerous growth factors and cytokines, including hepatocyte growth factor (HGF), keratinocyte growth factor, endothelial growth factor, epidermal growth factor, transforming growth factor-β1, intestinal trefoil factor, interleukin (IL)-1, and IL-2, are induced in both the intestinal lumen and submucosa, and these factors cooperatively stimulate epithelial mucosal repair. HGF, a major agent promoting hepatocyte proliferation, also modulates intestinal epithelial cell proliferation and migration, leading to the acceleration of intestinal mucosal repair. Additionally, the proteolytic activation of HGF, which is mediated by HGF activator, is essential for the regeneration of injured intestinal mucosa. Recently, several studies have shown that the administration of recombinant human HGF or HGF gene therapy abrogates disease severity in several animal models of inflammatory bowel disease (IBD). Recombinant human HGF will soon be available for administration to patients with fulminant hepatic failure. Although additional preclinical biological studies are required, HGF has the potential to be an important new treatment modality promoting intestinal mucosal repair in patients with IBD.

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References

  1. SB Hanauer DH Present (2003) ArticleTitleThe state of the art in the management of inflammatory bowel disease Rev Gastroenterol Disord 275 40453–62

    Google Scholar 

  2. WJ Sandborn SB Hanauer (1999) ArticleTitleAntitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety Inflamm Bowel Dis 5 119–33 Occurrence Handle10338381

    PubMed  Google Scholar 

  3. MS Murphy (1998) ArticleTitleGrowth factors and gastrointestinal tract Nutrition 14 771–4 Occurrence Handle10.1016/S0899-9007(98)00081-1 Occurrence Handle9785359

    Article  PubMed  Google Scholar 

  4. PL Beck DK Podolsky (1999) ArticleTitleGrowth factors in inflammatory bowel disease Inflamm Bowel Dis 5 44–60 Occurrence Handle10028449

    PubMed  Google Scholar 

  5. AU Dignass A Strum (2001) ArticleTitlePeptide growth factors in the intestine Eur J Gastroenterol Hepatol 13 763–70 Occurrence Handle10.1097/00042737-200107000-00002 Occurrence Handle11474304

    Article  PubMed  Google Scholar 

  6. AU Dignass (2001) ArticleTitleMechanisms and modulation of intestinal epithelial repair Inflamm Bowel Dis 7 68–77 Occurrence Handle11233665

    PubMed  Google Scholar 

  7. JMV Mammen JB Matthews (2003) ArticleTitleMucosal repair in the gastrointestinal tract Crit Care Med 31 S532–7 Occurrence Handle10.1097/01.CCM.0000081429.89277.AF Occurrence Handle12907883

    Article  PubMed  Google Scholar 

  8. R Okamoto T Yajima M Yamazaki T Kanai M Mukai S Okamoto et al. (2002) ArticleTitleDamaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract Nat Med 8 1011–7 Occurrence Handle10.1038/nm755 Occurrence Handle12195435

    Article  PubMed  Google Scholar 

  9. R Okamoto M Watanabe (2004) ArticleTitleMolecular and clinical basis for the regeneration of human gastrointestinal epithelia J Gastroenterol 39 1–6 Occurrence Handle10.1007/s00535-003-1259-8 Occurrence Handle14767727

    Article  PubMed  Google Scholar 

  10. T Matsumoto R Okamoto T Yajima T Mori S Okamoto Y Ikeda et al. (2005) ArticleTitleIncrease of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine Gastroenterology 128 1851–67 Occurrence Handle10.1053/j.gastro.2005.03.085 Occurrence Handle15940621

    Article  PubMed  Google Scholar 

  11. E Gohda H Tsubouchi H Nakayama S Hirono K Takahashi M Koura et al. (1986) ArticleTitleHuman hepatocyte growth factor in plasma of patients with fulminant hepatic failure Exp Cell Res 166 139–50 Occurrence Handle10.1016/0014-4827(86)90514-8 Occurrence Handle3527727

    Article  PubMed  Google Scholar 

  12. E Gohda H Tsubouchi H Nakayama S Hirono O Sakiyama K Takahashi et al. (1988) ArticleTitlePurification and partial characterization of hepatocyte growth factor of a patient with fulminant hepatic failure J Clin Invest 81 414–9 Occurrence Handle3276728

    PubMed  Google Scholar 

  13. T Igawa S Kanda H Kanetake Y Saitoh A Ichihara Y Tomita et al. (1991) ArticleTitleHepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells Biochem Biophys Res Commun 174 831–8 Occurrence Handle10.1016/0006-291X(91)91493-V Occurrence Handle1704229

    Article  PubMed  Google Scholar 

  14. R Joplin T Hishida H Tsubouchi Y Daikuhara R Ayres JM Neuberger et al. (1992) ArticleTitleHuman intrahepatic biliary epithelial cells proliferate in vitro in response to human hepatocyte growth factor J Clin Invest 90 1284–9 Occurrence Handle1401065

    PubMed  Google Scholar 

  15. M Takahashi S Ota A Terano K Yoshiura M Matsumura Y Miwa et al. (1993) ArticleTitleHepatocyte growth factor induces mitogenic reaction to the rabbit gastric epithelial cells in primary culture Biochem Biophys Res Commun 191 528–34 Occurrence Handle10.1006/bbrc.1993.1250 Occurrence Handle8461010

    Article  PubMed  Google Scholar 

  16. AU Dignass K Lynch-Devaney DK Podolsky (1994) ArticleTitleHepatocyte growth factor/scatter factor modulates intestinal epithelial cell proliferation and migration Biochem Biophys Res Commun 202 701–9 Occurrence Handle10.1006/bbrc.1994.1987 Occurrence Handle8048940

    Article  PubMed  Google Scholar 

  17. ER Lacy (1988) ArticleTitleEpithelial restitution in the gastrointestinal tract J Clin Gastroenterol 10 IssueIDSuppl 72–7

    Google Scholar 

  18. W Feil E Wentzl P Vattay M Starlinger T Sogukoglu R Schiessel (1987) ArticleTitleRepair of rabbit duodenal mucosa after acid injury in vivo and in vitro Gastroenterology 92 1973–86 Occurrence Handle3569771

    PubMed  Google Scholar 

  19. R Moore S Carlson JL Madara (1989) ArticleTitleRapid barrier restitution in an in vitro model of intestinal epithelial injury Lab Invest 60 237–44 Occurrence Handle2915518

    PubMed  Google Scholar 

  20. SA McCormack MJ Viar LR Johnson (1992) ArticleTitleMigration of IEC-6 cells: a model for mucosal healing Am J Physiol 263G 426–35

    Google Scholar 

  21. A Nusrat C Delp J Madara (1992) ArticleTitleIntestinal epithelial restitution J Clin Invest 89 1501–11 Occurrence Handle1569187

    PubMed  Google Scholar 

  22. InstitutionalAuthorNamePart 1. Epithelial Restitution (2002) Gastrointestinal mucosal repair and experimental therapeutics CH Cho JY Wang (Eds) Front Gastrointest Res, vol. 25 Karger Basel

    Google Scholar 

  23. A Grenier S Chollet-Martin B Crestani C Delarche J El Benna A Boutten et al. (2002) ArticleTitlePresence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils Blood 99 2997–3004 Occurrence Handle10.1182/blood.V99.8.2997 Occurrence Handle11929792

    Article  PubMed  Google Scholar 

  24. P Koehne C William E Strauss R Schindler KU Eckardt C Buhrer (2000) ArticleTitleLack of hypoxic stimulation of VEGF secretion from neutrophils and platelets Am J Physiol Heart Circ Physiol 279 H817–24 Occurrence Handle10924082

    PubMed  Google Scholar 

  25. Y Oka DN Orth (1983) ArticleTitleHuman plasma epidermal growth factor/S61538-urogastrone is associated with blood platelets J Clin Invest 72 249–59 Occurrence Handle6603475

    PubMed  Google Scholar 

  26. RK Assoian Sporn MB. Type (1986) ArticleTitleS61538 transforming growth factor in human platelets: release during platelet degradation and action on vascular smooth muscle cells J Cell Biol 102 1217–23 Occurrence Handle10.1083/jcb.102.4.1217 Occurrence Handle3457014

    Article  PubMed  Google Scholar 

  27. KP Karey DA Sirbasku (1989) ArticleTitleHuman platelet-derived mitogens: subcellular locarilation of insulin-like growth factor I to the S61537-granule and release in response to thrombin Blood 74 1093–100 Occurrence Handle2752154

    PubMed  Google Scholar 

  28. DK Podolsky (1999) ArticleTitleInnate mechanisms of mucosal defense and repair: the best offense is a good defense Am J Physiol Gastrointest Liver Physiol 277 G495–9

    Google Scholar 

  29. M Matsuura K Okazaki A Nishio H Nakase H Tamaki K Uchida et al. (2005) ArticleTitleTherapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis Gastroenterology 128 975–86 Occurrence Handle10.1053/j.gastro.2005.01.006 Occurrence Handle15825079

    Article  PubMed  Google Scholar 

  30. AU Dignass S Tsunekawa DK Podolsky (1994) ArticleTitleFibroblast growth factors modulate intestinal epithelial cell growth and migration Gastroenterology 106 1254–62 Occurrence Handle7513666

    PubMed  Google Scholar 

  31. C Ciacci SE Lind DK Podolsky (1993) ArticleTitleTransforming growth factor beta regulation of migration in wounded rat intestinal epithelial monolayers Gastroenterology 105 93–101 Occurrence Handle8514065

    PubMed  Google Scholar 

  32. P Boros CM Miller (1995) ArticleTitleHepatocyte growth factor: a multifunctional cytokine Lancet 345 293–5 Occurrence Handle10.1016/S0140-6736(95)90279-1 Occurrence Handle7837864

    Article  PubMed  Google Scholar 

  33. R Zarnegar GK Michalopoulos (1995) ArticleTitleThe many faces of hepatocyte growth factor: from hepatopoiesis to haemetopoiesis J Cell Biol 129 1177–80 Occurrence Handle10.1083/jcb.129.5.1177 Occurrence Handle7775566

    Article  PubMed  Google Scholar 

  34. D Naka T Ishii Y Yoshiyama K Miyazawa H Hara T Hishida et al. (1992) ArticleTitleActivation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer J Biol Chem 267 20114–9 Occurrence Handle1328193

    PubMed  Google Scholar 

  35. T Shimomura M Ochiai J Kondo Y Morimoto (1992) ArticleTitleA novel protease obtained from FBS-containing culture supernatant that processes single-chain form hepatocyte growth factor to two-chain form in serum free culture Cytotechnology 8 219–29 Occurrence Handle1368819

    PubMed  Google Scholar 

  36. K Miyazawa T Shimomura A Kitamura J Kondo Y Morimoto N Kitamura (1993) ArticleTitleMolecular cloning and sequence analysis of the cDNA for a human serine protease responsible for activation of hepatocyte growth factor J Biol Chem 268 10024–8 Occurrence Handle7683665

    PubMed  Google Scholar 

  37. H Itoh R Hamasuna H Kataoka M Yamauchi K Miyazawa N Kitamura et al. (2000) ArticleTitleMouse hepatocyte growth factor activator gene: its expression not only in the liver but also in the gastrointestinal tract Biochim Biophys Acta 1491 295–301 Occurrence Handle10760594

    PubMed  Google Scholar 

  38. T Shimomura J Kondo M Ochiai D Naka K Miyazawa Y Morimoto et al. (1993) ArticleTitleActivation of the zymogen of hepatocyte growth factor activator by thrombin J Biol Chem 268 22927–32 Occurrence Handle8226803

    PubMed  Google Scholar 

  39. K Miyazawa T Shimomura D Naka N Kitamura (1994) ArticleTitleProteolytic activation of hepatocyte growth factor in response to tissue injury J Biol Chem 269 8966–70 Occurrence Handle8132634

    PubMed  Google Scholar 

  40. K Miyazawa T Shimomura N Kitamura (1996) ArticleTitleActivation of hepatocyte growth factor in the injured tissues is mediated by hepatocyte growth factor activator J Biol Chem 271 3615–8 Occurrence Handle10.1074/jbc.271.7.3615 Occurrence Handle8631970

    Article  PubMed  Google Scholar 

  41. T Hori A Ido H Uto S Hasuike A Moriuchi K Hayashi et al. (2004) ArticleTitleActivation of hepatocyte growth factor in monkey stomach following gastric mucosal injury J Gastroenterol 39 133–9 Occurrence Handle10.1007/s00535-003-1264-y Occurrence Handle15069619

    Article  PubMed  Google Scholar 

  42. T Shimomura K Denda A Kitamura T Kawaguchi M Kito J Kondo et al. (1997) ArticleTitleHepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor J Biol Chem 272 6370–6 Occurrence Handle10.1074/jbc.272.10.6370 Occurrence Handle9045658

    Article  PubMed  Google Scholar 

  43. H Itoh H Kataoka M Tomita R Hamasuna Y Nawa N Kitamura et al. (2000) ArticleTitleUpregulation of HGF activator inhibitor type 1 but not type 2 along with regeneration of intestinal mucosa Am J Physiol Gastrointest Liver Physiol 278 635–43

    Google Scholar 

  44. H Kataoka T Shimomura T Kawaguchi R Hamasuna H Itoh N Kitamura et al. (2000) ArticleTitleHepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA activity in the pericellular microenvironment J Biol Chem 275 40453–62 Occurrence Handle10.1074/jbc.M006412200 Occurrence Handle11013244

    Article  PubMed  Google Scholar 

  45. M Takahashi S Ota T Simada E Hamada T Kawabe T Okudaira et al. (1995) ArticleTitleHepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture J Clin Invest 95 1994–2003 Occurrence Handle7738166

    PubMed  Google Scholar 

  46. M Goke DK Podolsky (1996) ArticleTitleRegulation of the mucosal epithelial barrier Baillieres Clin Gastroenterol 10 393–405 Occurrence Handle10.1016/S0950-3528(96)90049-4 Occurrence Handle8905115

    Article  PubMed  Google Scholar 

  47. S Nishimura M Takahashi S Ota M Hirano H Hiraishi (1998) ArticleTitleHepatocyte growth factor accelerates restitution of intestinal epithelial cells J Gastroenterol 33 172–8 Occurrence Handle10.1007/s005350050066 Occurrence Handle9605945

    Article  PubMed  Google Scholar 

  48. A Nurstat CA Parkos AE Bacarra PJ Godowski C Delp-Archer EM Rosen et al. (1994) ArticleTitleHepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium J Clin Invest 93 2056–65 Occurrence Handle8182137

    PubMed  Google Scholar 

  49. S Kitamura S Kondo Y Shimomura K Isozaki S Kanayama Y Higashimoto et al. (2000) ArticleTitleExpression of hepatocyte growth factor and c-met in ulcerative colitis Inflamm Res 49 320–4 Occurrence Handle10959552

    PubMed  Google Scholar 

  50. M Srivastava D Zurakowski P Cheifetz A Leichtner A Bousvaros (2001) ArticleTitleElevated serum hepatocyte growth factor in children and young adults with inflammatory bowel disease J Pediatr Gastroenterol Nutr 33 548–53 Occurrence Handle10.1097/00005176-200111000-00007 Occurrence Handle11740227

    Article  PubMed  Google Scholar 

  51. M Matsuo G Shiota K Umeki H Kawasaki H Kojo K Miura (1997) ArticleTitleInduction of plasma hepatocyte growth factor in acute colitis of mice Inflamm Res 46 166–7 Occurrence Handle10.1007/s000110050161 Occurrence Handle9197986

    Article  PubMed  Google Scholar 

  52. CF Ortega-Cava S Ishihara K Kawashima MAK Rumi H Kazumori K Adachi et al. (2002) ArticleTitleHepatocyte growth factor expression in dextran sodium sulfate-induced colitis in rats Dig Dis Sci 47 2275–85 Occurrence Handle10.1023/A:1020195513193 Occurrence Handle12395901

    Article  PubMed  Google Scholar 

  53. CJ Xian R Couper GS Howarth LC Read NC Kallincos (2000) ArticleTitleIncreased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis Br J Cancer 82 945–52 Occurrence Handle10.1054/bjoc.1999.1023 Occurrence Handle10732770

    Article  PubMed  Google Scholar 

  54. H Itoh S Naganuma N Takeda S Miyata S Uchinokura T Fukushima et al. (2004) ArticleTitleRegeneration of injured intestinal mucosa is impaired in hepatocyte growth factor activator-deficient mice Gastroenterology 127 1423–35 Occurrence Handle10.1053/j.gastro.2004.08.027 Occurrence Handle15521012

    Article  PubMed  Google Scholar 

  55. I Okayasu S Hatakeyama M Yamada T Ohkusa Y Inagaki R Nakaya (1990) ArticleTitleA novel model in the induction of reliable experimental acute and chronic ulcerative colitis in mice Gastroenterology 98 694–702 Occurrence Handle1688816

    PubMed  Google Scholar 

  56. CO Elson RB Sartor GS Tennyson RH Riddell (1995) ArticleTitleExperimental models of inflammatory bowel disease Gastroenterology 109 1344–67 Occurrence Handle10.1016/0016-5085(95)90599-5 Occurrence Handle7557106

    Article  PubMed  Google Scholar 

  57. Y Tahara A Ido S Yamamoto Y Miyata H Uto T Hori et al. (2003) ArticleTitleHepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats J Pharmacol Exp Ther 307 146–51 Occurrence Handle10.1124/jpet.103.054106 Occurrence Handle12954797

    Article  PubMed  Google Scholar 

  58. MF Neurath I Russ BL Kelsall E Stuber W Strober (1995) ArticleTitleAntibodies to interleukin 12 abrogate established experimental colitis in mice J Exp Med 182 1281–90 Occurrence Handle10.1084/jem.182.5.1281 Occurrence Handle7595199

    Article  PubMed  Google Scholar 

  59. T Hibi H Ogata A Sakuraba (2002) ArticleTitleAnimal models of inflammatory bowel disease J Gastroenterol 37 409–17 Occurrence Handle10.1007/s005350200060 Occurrence Handle12108674

    Article  PubMed  Google Scholar 

  60. M Numata A Ido A Moriuchi ID Kim Y Tahara S Yamamoto et al. (2005) ArticleTitleHepatocyte growth factor facilitates the repair of large colonic ulcers in 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats Inflamm Bowel Dis 11 551–8 Occurrence Handle10.1097/01.MIB.0000164192.71381.5c Occurrence Handle15905702

    Article  PubMed  Google Scholar 

  61. T Kuroiwa E Kakishita T Hamano Y Kataoka Y Seto N Iwata et al. (2001) ArticleTitleHepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function J Clin Invest 107 1365–73 Occurrence Handle11390418

    PubMed  Google Scholar 

  62. K Oh Y Iimuro M Takeuchi Y Kaneda T Iwasaki N Terada et al. (2005) ArticleTitleAmeliorating effect of hepatocyte growth factor on inflammatory bowel disease in a murine model Am J Physiol Gastrointest Liver Physiol 288 G729–35 Occurrence Handle10.1152/ajpgi.00438.2004 Occurrence Handle15550554

    Article  PubMed  Google Scholar 

  63. RE Hammer SD Makita JA Richardson JP Tang JD Taurog (1990) ArticleTitleSpontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta2m: an animal model of HLA-B27-associated human disorders Cell 63 1099–112 Occurrence Handle10.1016/0092-8674(90)90512-D Occurrence Handle2257626

    Article  PubMed  Google Scholar 

  64. LG Arthur KA Kuenzler MZ Schwartz (2003) ArticleTitleHepatocyte growth factor ameliorates inflammatory bowel disease in a rat model J Gastrointest Surg 7 1062–8 Occurrence Handle10.1016/j.gassur.2003.09.014 Occurrence Handle14675716

    Article  PubMed  Google Scholar 

  65. LG Arthur MZ Schwartz KA Kuenzler R Birbe (2004) ArticleTitleHepatocyte growth factor treatment ameliorates diarrhea and bowel inflammation in a rat model of inflammatory bowel disease J Pediatr Surg 39 139–43 Occurrence Handle10.1016/j.jpedsurg.2003.10.001 Occurrence Handle14966727

    Article  PubMed  Google Scholar 

  66. Y Ohda K Hori T Tomita N Hida T Kosaka Y Fukuda et al. (2005) ArticleTitleEffects of hepatocyte growth factor on rat inflammatory bowel disease models Dig DIs Sci 50 914–21 Occurrence Handle10.1007/s10620-005-2664-z Occurrence Handle15906768

    Article  PubMed  Google Scholar 

  67. T Mukoyama T Kanbe R Murai Y Murawaki T Shimomura K Hashiguchi et al. (2005) ArticleTitleTherapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice Biochem Biophys Res Commun 329 1217–24 Occurrence Handle10.1016/j.bbrc.2005.01.166 Occurrence Handle15766556

    Article  PubMed  Google Scholar 

  68. WJ Sandborn BE Sands DC Wolf JF Valentine M Safdi S Katz et al. (2003) ArticleTitleRepifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial Aliment Pharmacol Ther 17 1355–64 Occurrence Handle10.1046/j.1365-2036.2003.01589.x Occurrence Handle12786629

    Article  PubMed  Google Scholar 

  69. A Sinha JMD Nightingale KP West J Berlanga-Acosta RJ Playford (2003) ArticleTitleEpidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis New Engl J Med 349 350–7 Occurrence Handle10.1056/NEJMoa013136 Occurrence Handle12878742

    Article  PubMed  Google Scholar 

  70. A Ido A Moriuchi ID Kim M Numata Y Nagata-Tsubouchi S Hasuike et al. (2004) ArticleTitlePharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein Hepatol Res 30 175–81 Occurrence Handle10.1016/j.hepres.2004.09.002 Occurrence Handle15588784

    Article  PubMed  Google Scholar 

  71. H Sakata H Takayama R Sharp JS Rubin G Merlino WJ LaRochelle (1996) ArticleTitleHepatocyte growth factor/scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers Cell Growth Differ 7 1513–23 Occurrence Handle8930401

    PubMed  Google Scholar 

  72. H Takayama WJ LaRochelle R Sharp T Otsuka P Kriebel M Anver et al. (1997) ArticleTitleDiverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor Proc Natl Acad Sci USA 94 701–6 Occurrence Handle10.1073/pnas.94.2.701 Occurrence Handle9012848

    Article  PubMed  Google Scholar 

  73. MI Gallego B Bierie L Hennighausen (2003) ArticleTitleTargeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways Oncogene 22 8498–508 Occurrence Handle10.1038/sj.onc.1207063 Occurrence Handle14627990

    Article  PubMed  Google Scholar 

  74. A Bell Q Chen MC DeFrances GK Michalopoulos R Zarnegar (1999) ArticleTitleThe five amino acid-deleted isoform of hepatocyte growth factor promotes carcinogenesis in transgenic mice Oncogene 18 887–95 Occurrence Handle10.1038/sj.onc.1202379 Occurrence Handle10023664

    Article  PubMed  Google Scholar 

  75. N Horiguchi H Takayama M Toyoda T Otsuka T Fukusato G Merlino et al. (2002) ArticleTitleHepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine Oncogene 21 1791–9 Occurrence Handle10.1038/sj.onc.1205248 Occurrence Handle11896611

    Article  PubMed  Google Scholar 

  76. FP Nooman T Otsuka S Bang MR Anver G Merlino (2000) ArticleTitleAccelerated ultraviolet radiation-induced carcinogenesis in hepatocyte growth factor/scatter factor transgenic mice Cancer Res 60 3738–43 Occurrence Handle10919643

    PubMed  Google Scholar 

  77. H Takayama WJ LaRochelle M Anver DE Bockman G Merlino (1996) ArticleTitleScatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development Proc Natl Acad Sci USA 93 5866–71 Occurrence Handle10.1073/pnas.93.12.5866 Occurrence Handle8650184

    Article  PubMed  Google Scholar 

  78. G Shiota H Kawasaki T Nakamura EV Schmidt (1995) ArticleTitleCharacterization of double transgenic mice expressing hepatocyte growth factor and transforming growth factor S61537 Res Commun Mol Pathol Pharmacol 90 17–24 Occurrence Handle8581343

    PubMed  Google Scholar 

  79. E Santoni-Rugiu KH Preisegger A Kiss T Audolfsson G Shiota EV Schmidt et al. (1996) ArticleTitleInhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model Proc Natl Acad Sci USA 93 9577–82 Occurrence Handle10.1073/pnas.93.18.9577 Occurrence Handle8790372

    Article  PubMed  Google Scholar 

  80. H Nakase K Okazaki Y Tabata M Ozeki N Watanabe M Ohana et al. (2002) ArticleTitleNew cytokine delivery system using gelatin microspheres containing interleukin-10 for experimental inflammatory bowel disease J Pharmacol Exp Ther 301 59–65 Occurrence Handle10.1124/jpet.301.1.59 Occurrence Handle11907157

    Article  PubMed  Google Scholar 

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  1. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Akio Ido & Hirohito Tsubouchi

  2. Second department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Masatsugu Numata & Mayumi Kodama

  3. Department of Digestive Disease and Life-style related Disease, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan

    Hirohito Tsubouchi

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  1. Akio Ido
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Ido, A., Numata, M., Kodama, M. et al. Mucosal repair and growth factors: recombinant human hepatocyte growth factor as an innovative therapy for inflammatory bowel disease. J Gastroenterol 40, 925–931 (2005). https://doi.org/10.1007/s00535-005-1705-x

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