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

被引：31
作者：
Oh, K
Iimuro, Y
Takeuchi, M
Kaneda, Y
Iwasaki, T
Terada, N
Matsumoto, T
Nakanishi, K
Fujimoto, J
机构：
[1] Hyogo Med Univ, Dept Surg 1, Nishinomiya, Hyogo 6638501, Japan
[2] Hyogo Med Univ, Dept Internal Med, Nishinomiya, Hyogo 6638501, Japan
[3] Hyogo Med Univ, Dept Pathol, Nishinomiya, Hyogo 6638501, Japan
[4] Hyogo Med Univ, Dept Immunol & Med Zool, Nishinomiya, Hyogo 6638501, Japan
[5] Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Osaka, Japan
来源：
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2005年 / 288卷 / 04期
关键词：
2,4,6-trinitrobenzene sulfonic acid; gene therapy;
D O I：
10.1152/ajpgi.00438.2004
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
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 cMet/ 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 beta, interferon-gamma, and tumor necrosis factor-alpha. 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.
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收藏
页码：G729 / G735
页数：7
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