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

胃肠道上皮屏障在将腔内抗原和病原体与下层组织隔室分离方面起着关键作用。在炎症性肠病（IBD）、缺血或手术损伤等病理情况下，上皮屏障受损和粘膜损伤与临床症状相关。因此，上皮屏障的有效修复对于确保粘膜稳态的重建是重要的。作为对损伤的反应，上皮细胞迁移和增殖以修复粘膜缺损。最近的研究已经确定了促解决介质，协调炎症的主动解决和损伤后的修复。本研究将探讨促溶解介质脂素A4 （LXA4）和溶解蛋白D1 （RvD1）激活上皮甲酰基肽受体2 （FPR2/ALX）促进上皮伤口愈合的机制。我建议采用体外和体内互补的实验方法，研究LXA4和RvD1对肠黏膜伤口修复的影响。了解促溶激动剂介导的FPR2结扎调节肠上皮修复的机制，不仅将从概念上推进我们对肠黏膜伤口愈合的认识，而且将有助于制定促进肠黏膜伤口修复的治疗策略。

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.