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

本研究旨在探讨胃溃疡愈合过程中转化生长因子-β1、转化生长因子-β1及多种细胞外基质蛋白的基因表达，包括胎儿型细胞外基质的Tenascin、EIIIA、EIIIB-纤维连接蛋白的表达。用100%醋酸造成大鼠胃溃疡后处死大鼠。从大鼠胃溃疡组织和正常胃组织(对照组)中提取RNA，用特异的cDNA探针进行Northern印迹分析。溃疡组织中转化生长因子-β1基因表达在第5~32天高于对照组(第5天和第18天达到高峰)，60天后基本恢复正常。溃疡组织中ECM的基因表达水平与转化生长因子-β1基因表达水平一致。在溃疡组织中，TGFbeta1在第5天出现在溃疡床的大部分炎性细胞中，在第18天出现在肉芽组织中的肌成纤维细胞中。与对照组相比，前列腺素E1类似物Ornoprostil能促进溃疡愈合并增加转化生长因子-β1mRNA的表达。相反，消炎痛延缓了溃疡愈合，降低了转化生长因子-β1mRNA的表达。溃疡组织中Tenascin基因的表达在12h开始升高，3d再次升高，5d达到高峰。胎儿型纤维连接蛋白基因在假手术组大鼠完整胃组织中未检测到表达，但在第5~32d在溃疡组织中有表达。提示转化生长因子-β1和胎儿型细胞外基质在胃溃疡愈合过程中可能起重要作用。

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.