Formyl peptide receptors as mediators of intestinal mucosal homeostasis

 描述（由申请人提供）：胃肠上皮作为动态屏障发挥作用，作为腔内容物和下层组织隔室之间的界面，因此对维持粘膜稳态至关重要。在肠道感染、炎症性肠病和缺血性损伤后观察到粘膜损伤。关键上皮屏障的破坏允许管腔内容物进入免疫特权区室，从而有助于疾病的发病机制。肠上皮细胞（IEC）对损伤的反应是迁移和增殖，以迅速覆盖裸露的表面并重建上皮屏障。在确定肠上皮中的N-甲酰肽受体（FPR 1和FPR 2）后，我们的研究表明FPR 1配体（包括内源性脂质/蛋白质和外源性微生物群）控制肠上皮的稳态和修复。因此，拟议的研究将进一步探索这些FPR配体控制粘膜屏障恢复的机制。拟议的研究不仅将提供一个更好地了解FPRs调节上皮修复的基本机制，而且还将有助于开发新的治疗策略，旨在促进受伤粘膜的愈合。

 DESCRIPTION (provided by applicant): The gastrointestinal epithelium functions as a dynamic barrier that serves as an interface between luminal contents and underlying tissue compartments, and is thus vital in maintaining mucosal homeostasis. Mucosal wounds have been observed following enteric infection, inflammatory bowel disease and ischemic insults. Disruption of the critical epithelial barrier allows access of luminal contents to immunologically privileged compartments thereby contributing to disease pathogenesis. In response to injury, intestinal epithelial cells (IEC) migrate and proliferate to rapidly cover denuded surfaces and re-establish the epithelia barrier. After identifying N-formyl peptide receptors (FPR1 and FPR2) in the intestinal epithelium, our studies suggest that FPR1 ligands including endogenous lipid/proteins and exogenous microbiota control intestinal epithelial homeostasis and repair. Thus, the proposed studies will further explore mechanisms by which these FPR ligands control restitution of the mucosal barrier. The proposed studies will not only provide a better understanding of basic mechanisms by which FPRs regulate epithelial repair, but will also aid in the development of new therapeutic strategies aimed at promoting healing of the injured mucosa.