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Background and purpose <p>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.</p> Methods <p>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&amp;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.</p> Results <p>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.</p> Conclusions <p>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.</p> Graphical abstract

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FXR overexpression promotes liver regeneration through inducing FGF2 activation in APAP-induced acute liver injury

  • 期刊论文

  • 发表日期：

    2026年3月29日

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  • Rui Wang,
  • Jiaqi Chen,
  • Wenyu Wang,
  • Xia Li,
  • Yating Xiao,
  • Yubo Shi,
  • Yifan Qv,
  • Changyuan Wang,
  • Ting Fu,
  • Qiang Meng

摘要

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.

Graphical abstract