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

本研究旨在探讨大鼠胃溃疡愈合过程中转化生长因子β 1（TGF-β 1）和各种细胞外基质（ECM）蛋白（包括胎儿型ECM，如腱生蛋白和EIIIA、EIIIB-纤维连接蛋白）的基因表达。用100%乙酸诱导大鼠胃溃疡模型，处死大鼠。从假手术大鼠胃溃疡组织和正常胃组织中提取RNA，用特异性cDNA探针进行北方杂交。溃疡组织TGF-β 1基因表达在第5 ~ 32天高于对照组（第5和18天达到高峰），60天后恢复正常。溃疡组织中ECM的基因表达与TGF-β 1的基因表达以相同的方式增加。在溃疡组织中，TGF β 1在第5天的溃疡床上的大多数炎性细胞中被发现，并且在第18天的肉芽组织中的肌成纤维细胞中被发现。与对照组相比，前列腺素E1类似物奥诺前列素可加速溃疡愈合并增加TGF-β 1 mRNA表达。吲哚美辛可延缓溃疡愈合，降低TGF-β 1 mRNA表达。Tenascin mRNA在溃疡组织中的表达在12小时即开始升高，第3天再次升高，第5天达到高峰。胎型纤连蛋白基因在假手术大鼠完整胃组织中未检测到表达，但在溃疡组织中出现，出现时间为第5 ~ 32天。这些结果提示TGF-β 1和胎儿型ECM可能在胃溃疡愈合中起关键作用。

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.