Molecularbiological research for gastric ulcer and cancer, Roles of growth factors and extracellular matrix Professor Assoc. Prof.

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The present study was undertaken to investigate the gene expressions of Transforming growth factor-beta1 (TGF-beta1) TGF-beta1 and various extracellular matrix (ECM) proteins including fetal types of ECM such as tenascin and EIIIA,EIIIB-fibronectin during gastric ulcer healing in rats. Rats were killed after the production of gastric ulcer induced by 100% acetic acid. RNA was extracted from gastric ulcerous tissues and intact gastric tissues of sham-operated rats (controls), and assayd by northern blot with specific cDNA probes. The ulcer was maximum on day 5, has decreased in size gradually, and scarred on day 60.The gene expression of TGF-beta1 in the ulcerous tissues was higher than in the controls during day 5 to 32 (peaks on day 5 and 18), and returned to normal after day 60. The gene expressions of ECM in the ulcerous tissues increased in the same manner as that of TGF-beta1. In ulcerous tissues, TGFbeta1 was found in most inflammatory cells on the ulcer bed on day 5, and in myofibroblasts in the granulation on day 18. Ornoprostil, a prostaglandin E1 analogue, accelerated ulcer healing and increased TGF-beta1 mRNA expressions compared with controls. In contrast, indomethacin delayd ulcer healing and decreased TGF-beta1 mRNA expressions. Tenascin mRNA levels in ulcerous tissues were increased at 12 hrs and incrase again on day 3, peaked on day 5. The gene expressions of fetal types of fibronectin were not detected in the intact gastric tissues of sham-operated rats, but appeared in the ulcerous tissues during day 5 to 32. these results suggest that TGF-beta1 and fetal type ECM may play a crucial role in gastric ulcer healing.