Sturm A, Sudermann T, Schulte K M, Goebell H, Dignass A U
Department of Gastroenterology, Division of Medicine, University of Essen, Essen, Germany.
Gastroenterology. 1999 Aug;117(2):368-77. doi: 10.1053/gast.1999.0029900368.
BACKGROUND & AIMS: Lysophosphatidic acid (LPA) is assumed to play an important role in the modulation of injury and tissue repair in nonepithelial tissues. The effects of LPA on intestinal epithelial wound repair in vitro and in vivo were characterized.
Effects of LPA on intestinal epithelial restitution and proliferation were assessed by using an in vitro wounding model with confluent intestinal epithelial cell line 6 (IEC-6) monolayers and colorimetric thiazolyl blue (MTT) assays. In addition, LPA signaling pathways were characterized. Effects of LPA on intestinal wound healing in vivo were studied by using the trinitrobenzene model of colitis in rats.
LPA significantly enhanced migration and inhibited cell proliferation of IEC-6 cells in vitro. The effects on intestinal epithelial cell migration and proliferation were mediated through transforming growth factor beta (TGF-beta)-independent pathways and binding to a G-protein receptor. In addition, LPA significantly ameliorated intestinal epithelial injury in the trinitrobenzene model of colitis in rats.
These findings suggest that LPA enhances intestinal epithelial wound healing by modulation of intestinal epithelial cell migration and proliferation through TGF-beta-independent pathways. Thus, exogenous administration of LPA may provide a new approach for modulating intestinal injury in vivo.
溶血磷脂酸(LPA)被认为在非上皮组织的损伤调节和组织修复中发挥重要作用。本研究对LPA在体外和体内对肠上皮伤口修复的影响进行了表征。
通过使用融合的肠上皮细胞系6(IEC-6)单层的体外创伤模型和比色噻唑蓝(MTT)测定法,评估LPA对肠上皮恢复和增殖的影响。此外,还对LPA信号通路进行了表征。通过使用大鼠结肠炎的三硝基苯模型,研究LPA对体内肠伤口愈合的影响。
LPA在体外显著增强IEC-6细胞的迁移并抑制其增殖。对肠上皮细胞迁移和增殖的影响是通过不依赖转化生长因子β(TGF-β)的途径并与G蛋白受体结合介导的。此外,LPA在大鼠三硝基苯结肠炎模型中显著改善了肠上皮损伤。
这些发现表明,LPA通过不依赖TGF-β的途径调节肠上皮细胞迁移和增殖,从而增强肠上皮伤口愈合。因此 exogenous administration of LPA may provide a new approach for modulating intestinal injury in vivo.(原文最后一句英文表述有误,正确译文为:因此,外源性给予LPA可能为体内调节肠道损伤提供一种新方法。) 外源性给予LPA可能为体内调节肠道损伤提供一种新方法。