Ortega-Cava Cesar F, Ishihara Shunji, Kawashima Kousaku, Rumi Mohammad A K, Kazumori Hideaki, Adachi Kyoichi, Kinoshita Yoshikazu
Department of Internal Medicine II, Shimane Medical University, Izumo, Japan.
Dig Dis Sci. 2002 Oct;47(10):2275-85. doi: 10.1023/a:1020195513193.
Hepatocyte growth factor (HGF), a potent inducer of cell migration with morphogenic and mitogenic actions was reported to have key roles in the repair of various tissues. In order to evaluate the role of HGF in the repair process of inflammatory bowel disease, we have investigated the HGF expression in a dextran sodium sulfate (DSS) colitis model. We randomly assigned rats to a colitis group or to a placebo group; the former received a 7-day course of 5% DSS (mw 5 kDa) in drinking water. DSS-induced severe colitis in rats manifested with weight loss, diarrhea, and intestinal bleeding. Animals were killed from day 1 through 7 and on days 9 and 14 after the end of DSS administration. After DSS was withdrawn, disease activity subsided gradually and HGF expression was significantly enhanced along with the augmented expression of IL-1beta, TNF-alpha, and cyclooxygenase-2, accompanied by an increased number of proliferating epithelial cells in colon. These findings suggest that proinflammatory cytokines and cyclooxygenase-2 may have an important role in the mucosal repair in inflammatory bowel disease through increased production of HGF.
肝细胞生长因子(HGF)是一种具有形态发生和促有丝分裂作用的强效细胞迁移诱导剂,据报道在各种组织的修复中起关键作用。为了评估HGF在炎症性肠病修复过程中的作用,我们在葡聚糖硫酸钠(DSS)结肠炎模型中研究了HGF的表达。我们将大鼠随机分为结肠炎组或安慰剂组;前者饮用含5% DSS(分子量5 kDa)的水,为期7天。DSS诱导的大鼠严重结肠炎表现为体重减轻、腹泻和肠道出血。在DSS给药结束后的第1天至第7天以及第9天和第14天处死动物。停用DSS后,疾病活动逐渐消退,HGF表达显著增强,同时IL-1β、TNF-α和环氧化酶-2的表达增加,结肠中增殖上皮细胞数量增多。这些发现表明,促炎细胞因子和环氧化酶-2可能通过增加HGF的产生在炎症性肠病的黏膜修复中起重要作用。