Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats
Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats
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DOI：
10.1124/jpet.103.054106
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发表时间：
2003-10-01
影响因子：
3.5
通讯作者：
Tsubouchi, H
中科院分区：
文献类型：
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作者：
Tahara, Y;Ido, A;Tsubouchi, H
肝细胞生长因子(HGF)调控肠上皮细胞的增殖和迁移，是肠道创面愈合的重要调节因子。在本研究中，我们观察了重组人肝细胞生长因子对体内结肠粘膜损伤的影响。用5%葡聚糖硫酸钠(DSS)灌胃7d诱导大鼠急性结肠炎，用1%DSS灌胃维持大鼠结肠炎。给药第5天，将释放重组人肝细胞生长因子的渗透压泵(200g/d)植入大鼠腹膜内。持续的HGF腹腔注射导致血清HGF水平升高和结肠粘膜中c-Met酪氨酸磷酸化。与模型治疗的大鼠相比，服用人类HGF的大鼠在结肠炎相关的体重减轻、大肠缩短和改善结肠侵蚀方面显示出减少。重组人肝细胞生长因子可促进大鼠皮肤上皮再生和细胞增殖。肝、肾、脾重量不受HGF影响。这些结果表明，HGF可加速DSS诱导的结肠炎大鼠的结肠粘膜修复，提示重组人HGF可能是促进溃疡性结肠炎患者肠道伤口愈合的一种有用的治疗工具。
Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration, serving as a critical regulator of intestinal wound healing. In this study, we examined the effect of administration of recombinant human HGF on colonic mucosal damage in vivo. Acute colitis was induced in rats by feeding with 5% dextran sulfate sodium (DSS) for 7 days, and colitis was subsequently maintained by feeding with 1% DSS. On the 5th day of DSS administration, osmotic pumps releasing recombinant human HGF ( 200 mug/day) were implanted into the peritoneum of the rats. Continuous intraperitoneal delivery of HGF led to both increased serum human HGF levels and c-Met tyrosine phosphorylation within the colonic mucosa. Compared with mock-treated rats, those administered human HGF showed a reduction in colitis-associated weight loss, large intestinal shortening, and improved colonic erosions. Enhanced epithelial regeneration and cellular proliferation were observed in rats treated with recombinant human HGF. The weights of the liver, kidneys, and spleen were not affected by HGF administration. These results indicate that HGF administration accelerates colonic mucosal repair in rats with DSS-induced colitis and suggest that recombinant human HGF may be a useful therapeutic tool to facilitate intestinal wound healing in patients with ulcerative colitis.