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Updated: Jan 24, 2026

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
HSC-specific knockdown of GGPPS alleviated CCl4-induced chronic liver fibrosis through mediating RhoA/Rock pathway
Shan-Shan Lai1,2, Xiao Fu2,3, Qi Cheng2
1Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University Nanjing 210023, China.
Abstract:
Hepatic stellate cells (HSCs) play a critical role in the pathogenesis and reversal of liver fibrosis. Targeting HSCs is of great significance in the treatment of hepatic fibrosis, and has attracted wide attention of scholars. Here we demonstrated that expression of geranylgeranyldiphosphate synthase (GGPPS) predominantly increased in HSCs in murine fibrotic liver. HSC-specific knockdown of GGPPS using vitamin A-coupled liposome carrying siRNA-ggpps decreased activation of HSCs and alleviated fiber accumulation in vivo. Furthermore, our in vitro studies showed that GGPPS was up-regulated during HSCs activation in TGF-β1-dependent manner. Inhibition of GGPPS suppressed TGF-β1 induced F-actin reorganization and HSCs activation in LX-2 cells. Further, we found that GGPPS regulated HSCs activation and liver fibrosis possibly by enhancing RhoA/Rock kinase signaling. So its concluded that GGPPS promotes liver fibrosis by activating HSCs, which may represent a potential target for anti-fibrosis therapies.
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