Fenofibrate Inhibits Hepatic Stellate Cell Activation and Autophagy in Liver Fibrosis through the TGFΒ1/Smad3 and PPARα/cGAS/STING Pathways
Year: 2025
Type: article
Abstract: Liver fibrosis is a typical feature of abnormal liver structure and excessive collagen deposition.It is a chronic liver disease with some potential for reversal.Nonetheless, liver fibrosis remains a formidable clinical challenge.In this study, we investigated the anti-fibrotic mechanisms of fenofibrate and its therapeutic potential in liver fibrosis.Two liver fibrosis models were established in C57BL/6 mice: one induced by intraperitoneal carbon tetrachloride (CCl4) administration for 8 weeks, and the other by bile duct ligation (BDL) for 2 weeks.The BDL procedure involved exposing the common bile duct, followed by ligation and transection between the two tied points.Fenofibrate (50 and 100mg/kg) was administered via intraperitoneal injection three times per week.Gene and protein expression levels in tissues and cells were analyzed using RT-qPCR, Western blot, immunohistochemistry (IHC), immunofluorescence (IF), and other relevant techniques.Liver tissues were utilized for histological staining and transmission electron microscopy (TEM).The results showed that fenofibrate did not induce significant toxicity to the liver.Fenofibrate alleviated extracellular matrix (ECM) deposition in BDL and CCl4-mediated liver fibrosis models and regulated the balance between tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-2.Fenofibrate reduced hepatic stellate cells (HSCs) activation and autophagy through the peroxisome proliferator-activated receptor alpha (PPARα)/cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) and transforming growth factor beta 1 (TGFβ1)/smad family member 3(smad3) pathways.To summarize, fenofibrate alleviated liver fibrosis through suppressing HSCs activation.
Source: Pakistan Veterinary Journal
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $300
Awards: G6327923133, G6473872871
OpenAlex ID: W4413056516