Unveiling the role of Pafah1b3 in liver fibrosis:A novel mechanism revealed
10.1016/j.jpha.2024.101158
- Author:
Lifan LIN
1
;
Shouzhang YANG
;
Xinmiao LI
;
Weizhi ZHANG
;
Jianjian ZHENG
Author Information
1. Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,325000,China
- Publication Type:Journal Article
- Keywords:
Platelet-activating factor acetylhydrolase;
1B3;
Liver fibrosis;
Transforming growth factor-β signaling;
Hepatic stellate cells;
Ubiquitination
- From:
Journal of Pharmaceutical Analysis
2025;15(1):230-243
- CountryChina
- Language:English
-
Abstract:
Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3(Pafah1b3)in liver tissues from both carbon tetrachloride(CCl4)-treated mice and patients with cirrhosis.Deletion of Pafah 1b3 significantly attenuated CCl4-induced fibrosis,hepatic stellate cell(HSC)activation,and acti-vation of transforming growth factor-β(TGF-β)signaling.Mechanistically,PAFAH1B3 binds to mothers against decapentaplegic homolog 7(SMAD7),disrupting SMAD7's interaction with TGF-β receptor 1(TβR1),which subsequently decreases TβR1 ubiquitination and degradation.Pharmacological inhibition using 3-IN-P11,a specific Pafah1b3 inhibitor,conferred protective effects against CCl4-induced fibrosis in mice.Furthermore,Pafah 1b3 deficiency reduced hepatic inflammation.Overall,these results establish a pivotal role for Pafahl b3 in modulating TGF-β signaling and driving HSC activation.
