Hepatocyte growth factor (HGF)/c-met system has been thought to play an important role in the epithelial-mesenchymal interaction during the initial phase of gastric ulcer healing. However, in chronic course of gastric ulcer healing, the role of this factor remains largely unknown. In this study, we examined temporal changes of HGF/c-met expression by immunohistochemistry and in situ hybridization in an experimental ulcer induced by the application of acetic acid to the rat stomach. The rat normal gastric mucosa expressed c-met but not HGF in the surface epithelium. The expression of c-met in regenerating epithelium was weak at the active stage, but it increased the strength with the healing of ulcer progressing. The expression of HGF in the granulation tissue was undetectable at the active stage, but it increased the strength in concert with the c-met expression during the ulcer healing. In addition, c-met expressing cells appeared in granulation tissues from the active stage and reached a peak number at the early healing stage, which preceded the appearance of HGF expressing cells. At the scarring stage, expressions of both c-met and HGF decreased the intensity to the same level as normal gastric mucosa. The results of this study suggested that HGF/c-met system may work for the differentiation and maturation of regenerating epithelium and granulation tissues during ulcer healing.
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