Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed

Lifan Lin; Shouzhang Yang; Xinmiao Li; Weizhi Zhang; Jianjian Zheng

doi:10.1016/j.jpha.2024.101158

Volume 15 Issue 1

Feb. 2025

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Lifan Lin, Shouzhang Yang, Xinmiao Li, Weizhi Zhang, Jianjian Zheng. Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed[J]. Journal of Pharmaceutical Analysis, 2025, 15(1): 101158. doi: 10.1016/j.jpha.2024.101158

Citation:

Lifan Lin, Shouzhang Yang, Xinmiao Li, Weizhi Zhang, Jianjian Zheng. Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed[J]. Journal of Pharmaceutical Analysis, 2025, 15(1): 101158. doi: 10.1016/j.jpha.2024.101158

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Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed

doi: 10.1016/j.jpha.2024.101158

a. Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China;
b. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

Funds:

The project was supported by the National Natural Science Foundation of China (Grant No.: 81873576) and Wenzhou Municipal Science and Technology Bureau, China (Grant No.: Y20220023).

Received Date: Aug. 20, 2024
Accepted Date: Dec. 01, 2024
Rev Recd Date: Nov. 15, 2024
Publish Date: Dec. 09, 2024

Abstract

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 Pafah1b3 significantly attenuated CCl₄-induced fibrosis, hepatic stellate cell (HSC) activation, and activation 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, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.
- Platelet-activating factor acetylhydrolase 1B3,
- Liver fibrosis,
- Transforming growth factor-β signaling,
- Hepatic stellate cells,
- Ubiquitination

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References(43)

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