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

胃肠上皮屏障在将管腔抗原和病原体与下层组织隔室分离中起关键作用。在病理条件如炎性肠病（IBD）、缺血或手术损伤中观察到的上皮屏障受损和粘膜伤口与临床症状相关。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。作为对损伤的响应，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消退介质，其协调炎症的主动消退和损伤后的修复。本提案中的研究将探讨促消退介质脂氧素A4（LXA 4）和消退素D1（RvD 1）激活上皮甲酰肽受体2（FPR 2/ALX）以促进上皮伤口闭合的机制。本研究拟采用体内外互补的实验方法研究LXA 4和RvD 1对肠粘膜损伤修复的影响。了解FPR 2通过促消退激动剂结扎调节肠上皮修复的机制不仅将在概念上推进我们对肠粘膜伤口闭合的认识，而且还将有助于开发促进肠粘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.