HEPATOCYTE GROWTH-FACTOR IS THE MOST POTENT ENDOGENOUS STIMULANT OF RABBIT GASTRIC EPITHELIAL-CELL PROLIFERATION AND MIGRATION IN PRIMARY CULTURE

被引:147
|
作者
TAKAHASHI, M
OTA, S
SHIMADA, T
HAMADA, E
KAWABE, T
OKUDAIRA, T
MATSUMURA, M
KANEKO, N
TERANO, A
NAKAMURA, T
OMATA, M
机构
[1] UNIV TOKYO,FAC MED,DEPT PATHOL,TOKYO 113,JAPAN
[2] DOKKYO UNIV,SCH MED,DEPT MED 2,MIBU,TOCHIGI 32102,JAPAN
[3] OSAKA UNIV,SCH MED,CTR BIOMED RES,OSAKA 565,JAPAN
来源
JOURNAL OF CLINICAL INVESTIGATION | 1995年 / 95卷 / 05期
关键词
HEPATOCYTE GROWTH FACTOR; GASTRIC EPITHELIAL CELL; PROLIFERATION; RESTITUTION; NORTHERN BLOT HYBRIDIZATION;
D O I
10.1172/JCI117884
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:1994 / 2003
页数:10
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