Oh Koushi, Iimuro Yuji, Takeuchi Masaharu, Kaneda Yasufumi, Iwasaki Tsuyoshi, Terada Nobuyuki, Matsumoto Takayuki, Nakanishi Kenji, Fujimoto Jiro
First Dept. of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G729-35. doi: 10.1152/ajpgi.00438.2004. Epub 2004 Nov 18.
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 -1beta, 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.
肝细胞生长因子（HGF）是一种多功能细胞因子，可加速肠上皮细胞增殖。我们研究了HGF对三硝基苯磺酸诱导的结肠炎小鼠的影响，该模型在临床和分子水平上与克罗恩病相似。将患有结肠炎的小鼠反复进行人HGF cDNA的肌肉注射转染。评估体重、存活率、组织病理学、促炎细胞因子mRNA和白细胞浸润情况。用HGF cDNA治疗可诱导肠c-Met/HGF受体的酪氨酸磷酸化，抑制细胞凋亡，并促进肠上皮细胞的有丝分裂，加速肠上皮修复并抑制炎症。用HGF cDNA转染可显著抑制肠道中辅助性T细胞1细胞因子如白细胞介素-12和-1β、干扰素-γ和肿瘤坏死因子-α的mRNA表达。HGF基因转移减少了肠上皮中总T细胞和CD4阳性T细胞、中性粒细胞的数量以及髓过氧化物酶活性，还防止了体重减轻并提高了存活率。HGF可能对控制炎症性肠病有用。
