Formyl peptide receptors as mediators of intestinal mucosal homeostasis

甲酰基肽受体作为肠粘膜稳态调节剂

基本信息

批准号：
9181392
负责人：
ASMA NUSRAT
金额：
$ 62.01万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2020-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9181392
关键词：
Acute Address Agonist Animals Applications Grants Bacteria Base Sequence Biochemical Biological Biological Assay Biopsy Bone Marrow Transplantation Cell Line Cell Proliferation Colitis Communities Complement Data Development Disease Employee Strikes Enteral Epithelial Epithelial Cells Epithelium Exhibits FPR1 gene FPR2 gene Gastrointestinal tract structure Homeostasis Immune Immunofluorescence Immunologic Immunologics Impaired wound healing Impairment In Vitro Infection Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Injury Intestinal Mucosa Intestines Investigation Ischemia Knockout Mice Label Ligands Ligation Link Lipids Mechanics Mediating Mediator of activation protein Microbe Modeling Monitor Mucous Membrane Mus Mutant Strains Mice Natural regeneration Operative Surgical Procedures Oxidation-Reduction Pathogenesis Pathologic Pattern recognition receptor Peptides Perception Plant Resins Play Process Proliferating Property Proteins Proteomics Receptor Activation Recovery Resolution Role S-nitro-N-acetylpenicillamine Signal Transduction Structure Surface Surgical Injuries Taxonomy Technology Therapeutic Agents Tissues Western Blotting Wild Type Mouse Wound Healing cell motility experimental study fMet-Leu-Phe receptor gastrointestinal epithelium gut microbiota healing in vivo injured injury and repair intestinal epithelium knock-down lipid mediator lipoxin A4 microbial community microbiota migration mutant novel therapeutic intervention novel therapeutics protein complex public health relevance receptor receptor function repaired response response to injury signal recognition particle receptor small molecule wound wound closure

项目摘要

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.

描述（由适用提供）：胃肠道上皮功能作为动态屏障，是腔内内容物和基础组织室之间的界面，因此对于维持粘膜稳态至关重要。肠道感染，炎症性肠病和缺血性损伤后，已经观察到粘膜伤口。临界上皮屏障的破坏允许将腔内容物访问免疫特权隔室，从而有助于疾病发病机理。为了响应损伤，肠上皮细胞（IEC）迁移并增殖至迅速覆盖的表面并重新建立上皮屏障。在鉴定出肠上皮的N-甲基肽受体（FPR1和FPR2）之后，我们的研究表明，包括内源性脂质/蛋白质和外源性微生物群控制肠上皮上皮上皮稳态和修复在内的FPR1配体。这是拟议的研究将进一步探索这些FPR配体控制粘膜屏障的机制。拟议的研究不仅将更好地理解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受伤粘膜治愈的新治疗策略。