Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.
Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.
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DOI：
10.1172/jci117884
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发表时间：
1995-05
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影响因子：
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通讯作者：
Morio Takahashi;S. Ota;T. Shimada;E. Hamada;T. Kawabe;T. Okudaira;M. Matsumura;Nobuyuki Kaneko;A. Terano;Toshikazu Nakamura;M. Omata
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文献类型：
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作者：
Morio Takahashi;S. Ota;T. Shimada;E. Hamada;T. Kawabe;T. Okudaira;M. Matsumura;Nobuyuki Kaneko;A. Terano;Toshikazu Nakamura;M. Omata
各种生长因子被认为参与胃粘膜修复。我们前期的研究表明，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，几种生长因子的最大增殖效应和最佳浓度的比较显示，HGF是胃上皮细胞的最有效的有丝分裂原，就像肝细胞的情况一样。使用圆形伤口复原模型评估胃上皮细胞单层的复原。HGF是最有效的促进胃上皮恢复的药物。结合试验显示HGF与胃上皮细胞上的受体特异性结合。北方印迹分析证实胃上皮细胞表达特异性HGF受体mRNA（c-met），而胃成纤维细胞不表达。为了研究内源性HGF的产生，我们确定了胃成纤维细胞条件培养基对上皮细胞增殖和恢复的影响。条件培养基产生类似的作用，以肝细胞生长因子和其活性被中和的抗肝细胞生长因子抗体。此外，HGF mRNA在胃成纤维细胞中表达，而在胃上皮细胞中不表达。我们的免疫组化研究证实了这些在体外的数据，通过展示HGF的存在和本地化的人天然胃粘膜。HGF定位于胃溃疡周围上皮细胞层下的成纤维细胞。这些结果表明，肝细胞生长因子可能是一个强大的内源性促进胃上皮细胞增殖和迁移，并可能有助于通过旁分泌机制的胃粘膜修复。
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.