Speaker: Chuan Wu, MD, PhD, National Cancer Institute, National Institutes of Health

Time: 16:00-17:00 p.m., May 16, 2024, GMT+8

Venue: Rm B117, Research Complex #2, PKU

Abstract: 

The gut and liver are recognized to mutually communicate through the biliary tract, portal vein and systemic circulation. However, it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy, transcriptomic and proteomic profiling, we identified pigment epithelium-derived factor (PEDF), a liver-derived soluble Wnt inhibitor, that restrains intestinal stem cell (ISC) hyperproliferation to maintain gut homeostasis by suppressing the Wnt/b-catenin signaling pathway. Further, we found that microbial danger signals resulting from intestinal inflammation can be sensed by the liver, leading to the repression of PEDF production through peroxisome proliferator-activated receptor-a (PPARa). This repression liberates ISC proliferation to accelerate tissue repair in the gut. Additionally, treating mice with fenofibrate, a clinical PPARa agonist used for hypolipidemia, enhances colitis susceptibility due to PEDF activity. Therefore, we have identified a distinct role for PEDF in calibrating ISC expansion for intestinal homeostasis through reciprocal interactions between the gut and liver.

Source: College of Future Technology, PKU