The Microbial Metabolite Sensor Pregnane X Receptor (PXR) Restrains Fibroblasts from Promoting Gastrointestinal Inflammation and Fibrosis in Mice
Abstract
Fibrosis contributes to intestinal strictures and obstruction in 30–50% of Crohn's disease patients. The pathogenesis of intestinal fibrosis is incompletely understood and has virtually no effective treatments. The pregnane X receptor (PXR), a xenobiotic receptor involved in detoxification responses, has recently been identified as a modulator of fibrosis in hepatic stellate cells. Of the number of foreign ligands for the PXR, the tryptophan metabolite indole‐3‐propionic acid (IPA) produced by the intestinal commensal Clostridium sporogenes can bind to the PXR to mediate signalling events that protect intestinal barrier function. The role of the PXR in intestinal fibrosis and if microbial metabolite sensing can affect intestinal fibrotic responses is unknown.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2017
- Source ID
- 10.1096/fasebj.31.1_supplement.1051.2
Entities
People
- Kyle Flannigan
- Laurie Alston
- Simon A Hirota
- Sridhar Mani
- Thomas Chang
Organizations
- Albert Einstein College of Medicine
- United States Department of Defense
- University of British Columbia
- University of Calgary