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.

Public Health Relevance

The lining of the gastrointestinal tract plays an important role in immune defense, which can be significantly compromised by conditions such as inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. The grant application will address the role of formyl peptide receptor ligands that include endogenous ligands and microbiota in regulating healing of the intestinal mucosa after injury. Thus, these studies will not only provide a better understanding of basic function of these receptors, but will also facilitate the development of novel therapeutic strategies aimed at promoting mucosal wound repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK089763-07
Application #
9386748
Study Section
Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
Project Start
Project End
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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