权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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。