Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach.
Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach.
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肝细胞生长因子是调节胃中前列腺素抗溃疡作用的关键。
DOI：
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发表时间：
1996
影响因子：
15.9
通讯作者：
M. Omata
中科院分区：
文献类型：
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作者：
M. Takahashi;S. Ota;Y. Hata;Y. Mikami;N. Azuma;T. Nakamura;A. Terano;M. Omata
尽管甘草素（PGs）的临床疗效，特别是对非甾体类抗胃溃疡药物引起的胃粘膜损伤的疗效，得到广泛认可，但除抑酸作用外，其作用机制尚不清楚。本研究建立了人胃成纤维细胞的原代培养体系，并证实PG可诱导胃成纤维细胞表达肝细胞生长因子（HGF），而这种诱导作用是由PG特异性受体EP2或EP4介导的。由于HGF以旁分泌方式促进胃上皮细胞的修复和保护，因此假定PG的一些有益作用可能由HGF介导。为了证实这一假设，我们建立了一个简化的体外培养胃粘膜模型，该模型由胃上皮细胞和胃成纤维细胞组成。使用该模型，我们进行了圆形伤口恢复试验。PGE1能明显促进肝细胞的修复，而抗HGF抗体可完全抑制PGE1的修复作用，表明PGE1的这种作用是由HGF介导的。为了证实这些体外实验数据，我们进一步证实了在非甾体类抗肿瘤药物诱导的胃溃疡边缘，HGF mRNA表达下调，而在这些边缘，PG应该被耗尽。综上所述，我们认为胃成纤维细胞是PGs的新靶点，人胃成纤维细胞产生的HGF可能是PGs抗胃溃疡作用的关键因素。
Although the clinical efficacy of prostaglandins (PGs), especially on gastric mucosal injuries induced by nonsteroidal antiinflammatory drugs, is widely appreciated, their mechanism of action, apart from acid suppression, is quite unclear. In this study, we have established a primary culture system of human gastric fibroblasts and clearly demonstrated that PGs strongly induce the expression of hepatocyte growth factor (HGF) in the fibroblasts, which is mediated by PGE specific receptor, EP2 or EP4. Since HGF facilitates repair and protection of gastric epithelial cells in a paracrine manner, it is assumed that some of the beneficial effects of PGs may be mediated by HGF. To confirm this assumption, we established a simplified in vitro culture gastric mucosal model which consists of gastric epithelial cells and gastric fibroblasts. Using the model, we performed a round wound restitution assay. PGE1 remarkably accelerated restitution which was completely inhibited by anti-HGF antibody, indicating that the action was mediated by HGF. To confirm these in vitro data, we further demonstrated that HGF mRNA expression is downregulated at the edges of nonsteroidal antiinflammatory drug-induced gastric ulcers where PGs should be depleted. In summary, we proposed that gastric fibroblasts are newly recognized targets of PGs, and HGF produced by human gastric fibroblasts may be a key factor for anti-ulcer action of PGs in the stomach.