Influence of Formyl Peptide Receptor 2 ligands Lipoxin A4 and Resolvin D1 on intestinal epithelial wound closure

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The gastrointestinal epithelial barrier plays a pivotal role in separating luminal antigens and pathogens from underlying tissue compartment. Epithelial barrier compromise and mucosal wounds seen in pathologic conditions such as inflammatory bowel disease (IBD), ischemia or surgical injury are associated with clinical symptoms. Thus, efficient repair of the epithelial barrier is important in ensuring re-establishment of mucosal homeostasis. In response to injury, epithelial cells migrate and proliferate to repair the mucosal defect. Recent studies have identified pro-resolving mediators that coordinate active resolution of inflammation and repair following injury. Studies in this proposal will investigate mechanisms by which the pro-resolving mediators lipoxin A4 (LXA4) and resolvin D1 (RvD1) activate epithelial formyl peptide receptor 2 (FPR2/ALX) to promote epithelial wound closure. I propose to use complementary in vitro and in vivo experimental approach to investigate the influence of LXA4 and RvD1 on intestinal mucosal wound repair. Understanding the mechanisms by which FPR2 ligation by pro-resolving agonists regulates intestinal epithelial repair will not only conceptually advance our knowledge of intestinal mucosal wound closure, but will also facilitate in the development of therapeutic strategies to promote intestinal mucosal wound repair.