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Updated: Feb 15, 2026

Seven Steps to Stellate Cells
Published on: May 10, 2011
Targeting the FAPα/Integrin αvβ1 complex attenuates hepatic stellate cell activation and liver fibrosis
Chun Guan1, Nuo Cheng1, Yu Tong1
1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 211198, PR China.
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 CCl4-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.
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