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肝细胞生长因子是原代培养中兔胃上皮细胞增殖和迁移的最有效内源性刺激物。

Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

作者信息

Takahashi M, Ota S, Shimada T, Hamada E, Kawabe T, Okudaira T, Matsumura M, Kaneko N, Terano A, Nakamura T

机构信息

Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.

出版信息

J Clin Invest. 1995 May;95(5):1994-2003. doi: 10.1172/JCI117884.

DOI:10.1172/JCI117884
PMID:7738166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC295775/
Abstract

Various growth factors are suggested to be involved in gastric mucosal repair. Our previous studies have shown that exogenous hepatocyte growth factor (HGF) has a proliferative effect on gastric epithelial cells. In the present study, comparison of the maximum proliferative effects and the optimum concentrations of several growth factors revealed that HGF was the most potent mitogen for gastric epithelial cells, as is the case for hepatocytes. Restitution of gastric epithelial cell monolayers was assessed using a round wound restitution model. HGF was the most effective agent for facilitating gastric epithelial restitution among those tested. A binding assay revealed specific binding of HGF to its receptor on gastric epithelial cells. Northern blot analysis confirmed the expression of specific HGF receptor mRNA (c-met) by gastric epithelial cells but not by gastric fibroblasts. To investigate endogenous HGF production, we determined the effect of gastric fibroblast-conditioned medium on epithelial proliferation and restitution. The conditioned medium produced similar effects to HGF and its activity was neutralized by an anti-HGF antibody. In addition, expression of HGF mRNA was detected in gastric fibroblasts but not in gastric epithelial cells. Our immunohistochemical study confirmed these in vitro data by means of demonstrating the existence and localization of HGF at human native gastric mucosa. HGF was localized at fibroblasts under the epithelial cell layer around gastric ulcers. These results suggest that HGF may be a potent endogenous promotor of gastric epithelial cell proliferation and migration, and may contribute to gastric mucosal repair through a paracrine mechanism.

摘要

多种生长因子被认为参与胃黏膜修复。我们之前的研究表明，外源性肝细胞生长因子（HGF）对胃上皮细胞有增殖作用。在本研究中，对几种生长因子的最大增殖效应和最佳浓度进行比较后发现，HGF是对胃上皮细胞最有效的促分裂原，对肝细胞也是如此。使用圆形伤口修复模型评估胃上皮细胞单层的修复情况。在测试的因子中，HGF是促进胃上皮修复最有效的因子。结合试验显示HGF与其在胃上皮细胞上的受体有特异性结合。Northern印迹分析证实胃上皮细胞而非胃成纤维细胞表达特异性HGF受体mRNA（c-met）。为了研究内源性HGF的产生，我们测定了胃成纤维细胞条件培养基对上皮细胞增殖和修复的影响。该条件培养基产生了与HGF相似的作用，其活性可被抗HGF抗体中和。此外，在胃成纤维细胞中检测到了HGF mRNA的表达，但在胃上皮细胞中未检测到。我们的免疫组织化学研究通过证明HGF在人天然胃黏膜中的存在和定位，证实了这些体外实验数据。HGF定位于胃溃疡周围上皮细胞层下方的成纤维细胞。这些结果表明，HGF可能是胃上皮细胞增殖和迁移的一种有效的内源性促进因子，并可能通过旁分泌机制促进胃黏膜修复。

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Biochem Biophys Res Commun. 1993 Mar 15;191(2):528-34. doi: 10.1006/bbrc.1993.1250.
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Paracrine control of gastric epithelial cell growth in culture by transforming growth factor-alpha.
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Endoscopic application of EGF-chitosan hydrogel for precipitated healing of GI peptic ulcers and mucosectomy-induced ulcers.EGF-壳聚糖水凝胶在胃肠道消化性溃疡和黏膜切除术后溃疡愈合中的内镜应用。
J Mater Sci Mater Med. 2014 Feb;25(2):573-82. doi: 10.1007/s10856-013-5088-x. Epub 2013 Dec 14.
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Hepatocyte growth factor stimulates the migration of gastric epithelial cells by altering the subcellular localization of the tight junction protein ZO-1.肝细胞生长因子通过改变紧密连接蛋白 ZO-1 的细胞内定位来刺激胃上皮细胞的迁移。
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Growth regulation of rabbit gastric epithelial cells and protooncogene expression.兔胃上皮细胞的生长调节与原癌基因表达
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