MassIVE MSV000091409

Partial Public PXD040586

Gut-liver axis calibrates intestinal stem cell fitness via PEDF

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Description

The gut and liver have been recognized to mutually communicate through the biliary tract, portal vein and systemic circulation, but it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy, transcriptomics and proteomics profiling, we identified pigment epithelium-derived factor (PEDF), as a liver-derived soluble Wnt inhibitor, that can restrain intestinal stem cells (ISC) hyperproliferation for gut homeostasis by competing with Wnt ligands and suppressing Wnt/beta-catenin signaling pathway. In turn, microbial danger signals from intestinal inflammation can be sensed by the liver to repress PEDF production via peroxisome proliferator-activated receptor-alpha (PPAR alpha), liberating ISC proliferation to accelerate tissue repair in the gut. Further, treatment of mice with fenofibrate, a clinical agent of PPARalpha agonist for hypolipidemia enhances the susceptibility of colitis via PEDF activity. Therefore, we identified a distinct role of PEDF to calibrate ISC expansion for intestinal homeostasis via reciprocal interactions between the gut and liver. [doi:10.25345/C5GH9BK5M] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: PEDF ; stem cell ; gut-liver axis

Contact

Principal Investigators:
(in alphabetical order) 		Yan Wang, NIH/NIDCR, United States
Submitting User: Ywang16

Publications

Kim G, Chen Z, Li J, Luo J, Castro-Martinez F, Wisniewski J, Cui K, Wang Y, Sun J, Ren X, Crawford SE, Becerra SP, Zhu J, Liu T, Wang S, Zhao K, Wu C.
Gut-liver axis calibrates intestinal stem cell fitness.
Cell. 2024 Feb 15;187(4):914-930.e20. Epub 2024 Jan 26.

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