Modulation of intestinal epithelial wound healing in vitro and in vivo by lysophosphatidic acid

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. Methods: 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. Results: 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. Conclusions: 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.