Gut-liver axis calibrates intestinal stem cell fitness via PEDF
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA951698 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24055930_1.fastq.gz | Fastqsanger.gz | |||
| SRR24055930_2.fastq.gz | Fastqsanger.gz | |||
| SRR24055931_1.fastq.gz | Fastqsanger.gz | |||
| SRR24055931_2.fastq.gz | Fastqsanger.gz | |||
| SRR24055932_1.fastq.gz | Fastqsanger.gz |
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Project 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.
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