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Updated: Mar 31, 2026
Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
FXR overexpression promotes liver regeneration through inducing FGF2 activation in APAP-induced acute liver injury
Rui Wang1, Jiaqi Chen1, Wenyu Wang1
1Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.
Background And Purpose:
Acetaminophen (APAP)-induced hepatotoxicity represents a critical medical emergency due to the rapid progression. To date, practical and feasible early interventions are limited. This study aimed to explore whether farnesoid X receptor (FXR, NR1H4) alleviates APAP-induced acute liver injury and whether this effect is mediated by fibroblast growth factor 2 (FGF2) activation to promote liver regeneration.
Methods:
The difference in FXR expression between healthy subjects and patients with APAP-induced acute liver injury was analyzed through the Gene Expression Omnibus (GEO) database. The adeno-associated virus-8-mediated FXR (AAV-FXR) was injected through the tail vein into mice to establish the mouse FXR-overexpressed model. pcDNA-FXR, siFXR or siFGF2 plasmids were transfected into AML-12 cells. H&E staining, quantitative real-time PCR, Western blotting, immunofluorescence staining, DCFH-DA staining, and TUNEL staining were applied to determine the effects of FXR and FGF2.
Results:
FXR was significantly reduced in hepatic tissues of patients with APAP-induced acute liver injury compared to normal hepatic tissues. FXR overexpression attenuated APAP-induced liver injury by inhibiting inflammation, oxidative stress and apoptosis, while promoting liver regeneration. Furthermore, FXR overexpression upregulated FGF2 expression, and its pro-regenerative effect against APAP-induced acute liver injury is dependent on FGF2. In contrast, FXR or FGF2 knockdown resulted in opposite effects.
Conclusions:
FXR alleviated APAP-induced acute liver injury by mitigating inflammation, oxidative stress and apoptosis, as well as promoting liver regeneration. This pro-regenerative effect of FXR is dependent on FGF2 activation.
