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

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

Transgenic overexpression of Reg protein caused gastric cell proliferation and differentiation along parietal cell and chief cell lineages

“…These data suggest a new role of Reg protein in the differentiation of gastric progenitor cells along chief cell and parietal cell lineages in vivo. So far, several growth factors have been implicated in the regulation of gastric epithelial cell growth, largely based on studies with cells cultured in vitro (Chen et al, 1991;Rutten et al, 1991Rutten et al, , 1993Yoshiura et al, 1994;Takahashi et al, 1995). Among these growth factors, TGFa is the only one that was shown to exhibit a drastic effect on gastric cell proliferation and differentiation in an in vivo transgenic mouse model Takagi et al, 1992;Sharp et al, 1995).…”

Distribution of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) in Human Tissues: Cellular Surface Localization of HAI-1 in Simple Columnar Epithelium and Its Modulated Expression in Injured and Regenerative Tissues

“…This hypothesis may agree with the fact that the cells which expressed HAI-1 protein in this study are susceptible to HGF/SF. For example, HGF/SF is an important mitogen for the gastric, bile duct, and renal tubule epithelium (Kawaida et al 1994;Takahashi et al 1995;Matsumoto and Nakamura 1996;Kinoshita et al 1997) and Schwann cells (Kranoselsky et al 1994). However, another important target of HGF/SF, hepatocytes, did not express HAI-1 protein, and bronchial and alveolar epithelia, which are also susceptible to HGF/SF (Ohmichi et al 1996), expressed a very low level of HAI-1 protein.…”

Macro-environment of breast carcinoma: frequent genetic alterations in the normal appearing skins of patients with breast cancer

“…[14][15][16][17] It is well known that skin fibroblasts (dermis) and epidermal epithelial cells produce several of these growth factors. Recently, HGF, which is mainly produced by fibroblasts, has been identified as one of the most potent mitogenic factors for proliferation of epithelial cells in a variety of organs.…”

“…Recently, HGF, which is mainly produced by fibroblasts, has been identified as one of the most potent mitogenic factors for proliferation of epithelial cells in a variety of organs. [14][15] Genetic alterations with loss of tumor suppressor genes (TSGs) in the stromal cells may lead to subsequent abnormal production of growth factors with constant signal transduction in the epithelial cells. Macro-environment of breast carcinoma F Moinfar et al migration-stimulating factor (MSF), which is produced by both fetal and cancer patient fibroblasts, but not by adult fibroblasts.…”