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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/G729    most recent 00438.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Oh, K. Articles by Fujimoto, J. Search for Related Content PubMed PubMed Citation Articles by Oh, K. Articles by Fujimoto, J.

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Ameliorating effect of hepatocyte growth factor on inflammatory bowel disease in a murine model

¹First Department of Surgery and Departments of ³Internal Medicine, ⁴Pathology, and ⁵Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan; and ²Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka

Submitted 27 September 2004 ; accepted in final form 11 November 2004

Hepatocyte growth factor (HGF), a multifunctional cytokine, accelerates intestinal epithelial proliferation. We studied the effects of HGF in mice with trinitrobenzene sulfonic acid-induced colitis, which shows clinical and molecular resemblance to Crohn's disease. Mice with colitis repeatedly were transfected intramuscularly with human HGF cDNA. Weight, survival, histopathology, proinflammatory cytokine mRNAs, and leukocyte infiltration were assessed. Treatment with HGF cDNA induced tyrosine phosphorylation of intestinal c-Met/HGF receptors, inhibited apoptosis, and promoted mitosis in intestinal epithelial cells, accelerating intestinal epithelial restoration and suppressing inflammation. Transfection with HGF cDNA markedly suppressed intestinal mRNA expression of T-helper 1 cytokines such as interleukin-12 and -1, interferon-, and tumor necrosis factor-. Numbers of total and CD4-positive T cells, neutrophils, and myloperoxidase activity in intestinal epithelium were diminished by HGF gene transfer, which also prevented weight loss, and improved survival. HGF might prove useful for controlling inflammatory bowel disease.

2,4,6-trinitrobenzene sulfonic acid; gene therapy

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