Growth regulation of normal rabbit gastric epithelial cells in primary culture

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We investigated the mechanism of the growth regulation of normal gastric epithelial cells using primary culture system of rabbit gastric epithelial cells. Results of our research were as follows : 1. Growth of rabbit gastric epithelial cells was positively regulated by EGF,TGF alpha, insulin, and cAMP,while it was negatively regulated by TGF beta. 2. Proto-oncogenes, such as c-fos and c-myc, were induced by these growth factors, whether the extent of induction was not necessary correlated with the effects of these growth regulators on cell growth. 3. Although rhese cells possessed P2 purinergic receptors, ATP did not have any effects on cellgrowth with or without EGF.4. Hepatocyte growth factor (HGF) was the most potent stimulant of rabbit gastric epithelial proliferation and migration, compared with EGF,TGF alpha, and insulin. 5. Conditioned medium of rabbit gastric fibroblasts in primary culture stimulated growth and migration of epithelial cells, which was blocked by anti-rabbit HGF.6. A binding assay revealed specific binding of HGF on gastric epithelial cells. Northern blot analysis confirmed expression of the HGF specific receptor, c-met mRNA,in gastric epithelial cells but not in fibroblasts. 7. Expression of HGF mRNA was detected in gastric fibroblasts but not in epithelial cells. 8. Expression of HGF protein and mRNA was detected in human gastric ulcers.These results suggest that growth factors regulte the growth of gastric epithelial cells, though expression of c-fos and c-myc is not essential, and that HGF might be an important factor of the repair of the gastric mucosa.