Targeting the FAPα/Integrin αvβ1 complex attenuates hepatic stellate cell activation and liver fibrosis

Chun Guan, Nuo Cheng, Yu Tong, Yifei Li, Jiayi Liu, Haishan Luo, Shihao Liu, Jihai Chen, Cong Wang

Journal：BIOCHEMICAL PHARMACOLOGY

IF：6.5

DOI：10.1016/j.bcp.2026.117801

PMID：41687828

Published：2026-02-11

research field：分子生物学药物开发肝脏病学细胞信号转导纤维化研究

Abstract

Hepatic stellate cell (HSC) activation is central to liver fibrosis. Fibroblast activation protein α (FAPα) is highly expressed in activated HSCs, yet its regulatory role remains unclear. This study investigates the function and mechanism of FAPα in HSC activation and fibrosis progression. Using TGF-β1-induced LX2 cells and CCl 4 -induced mouse models, along with small-molecule inhibitors and multi-omics analyses, we found that inhibiting FAPα suppressed HSC activation, proliferation, migration, and ameliorated fibrosis. Notably, FAPα formed a functional complex with Integrin αvβ1 in activated HSCs. Dual inhibition of FAPα/Integrin αvβ1 more effectively attenuated HSC activation and fibrosis than single-agent treatment. Transcriptomic and proteomic studies revealed that the complex acts through the GPC3/FGF21 axis. This study identifies the FAPα/Integrin αvβ1 complex as a key regulator of liver fibrosis and provides a novel combinatory therapeutic strategy for anti-fibrotic drug development.

本文使用的Yeasen产品

相关产品

[36261ES]

Precast Protein Plus Gel, 12%, 10 wells, Bis-Tris 12%高分辨率预制胶(Bis-Tris)，10孔

[36259ES]

Precast Protein Plus Gel, 8%, 10 wells, Bis-Tris 8%高分辨率预制胶(Bis-Tris)，10孔

[36265ES]

Precast Protein Plus Gel, 8%, 15 wells, Bis-Tris 8%高分辨率预制胶(Bis-Tris)，15孔

[36263ES]

Precast Protein Plus Gel, 4-12%, 10 wells, Bis-Tris 4-12%高分辨率预制胶(Bis-Tris)，10孔

[36267ES]

Precast Protein Plus Gel, 12%, 15 wells, Bis-Tris 12%高分辨率预制胶(Bis-Tris)，15孔