Formyl peptide receptors as mediators of intestinal mucosal homeostasis

 描述(申请人提供)：胃肠道上皮起着动态屏障的作用，作为管腔内容物和底层组织间隔之间的接口，因此对维持粘膜内环境的稳定至关重要。在肠道感染、炎症性肠病和缺血性损伤后可观察到粘膜损伤。关键的上皮屏障的破坏允许腔内容物进入免疫特异室，从而促进疾病的发病。作为对损伤的反应，肠上皮细胞(IEC)迁移和增殖以快速覆盖裸露表面并重建上皮屏障。在鉴定了肠上皮细胞中的N-甲酰肽受体(FPR1和FPR2)后，我们的研究表明，FPR1配体包括内源性脂质/蛋白质和外源微生物区系，控制着肠上皮的动态平衡和修复。因此，拟议的研究将进一步探索这些FPR配体控制粘膜屏障重建的机制。拟议的研究不仅将提供更好的了解FPR调节上皮修复的基本机制，而且还将有助于开发旨在促进损伤粘膜愈合的新的治疗策略。

 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.