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MicroRNA-124 expression in Kupffer cells modulates liver injury by targeting IL-6/STAT3 signaling

Jinyu Wang1, Xueyun Zhang1, Jiajia Han1

  • 1Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Antiviral Research
|December 29, 2022
PubMed

Insights

Serum microRNA-124 (miR-124) predicts prognosis in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). MiR-124 reduces liver inflammation by inhibiting IL-6/STAT3 signaling, offering a potential therapeutic target for liver injury.

Area of Science:

  • Hepatology
  • Immunology
  • Molecular Biology

Background:

  • Chronic hepatitis B (CHB) and hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are significant causes of liver injury.
  • The precise mechanisms by which microRNA-124 (miR-124) influences liver inflammation in these conditions are not fully understood.

Purpose of the Study:

  • To investigate the role of miR-124 in liver inflammation and its potential as a predictive biomarker in HBV-ACLF.
  • To elucidate the molecular mechanism through which miR-124 regulates liver injury.

Main Methods:

  • Analysis of serum miR-124 levels in patients with HBV-ACLF.
  • Utilizing a mouse model of concanavalin A-induced acute liver injury.
  • Investigating the effect of miR-124 overexpression on interleukin-6 (IL-6) secretion and liver necrosis.
  • Identifying the direct target of miR-124 using molecular assays.

Main Results:

  • Serum miR-124 levels were found to be a compensatory predictive factor for organ failure and 28-day prognosis in HBV-ACLF patients.
  • In a mouse model, miR-124 was highly expressed in Kupffer cells and its overexpression reduced IL-6 secretion and liver necrosis.
  • MiR-124 was shown to directly target the 3'-untranslated region of signal transducer and activator of transcription 3 (STAT3), inhibiting the IL-6/STAT3 signaling pathway.
  • This inhibition led to reduced pro-inflammatory Kupffer cell polarization.

Conclusions:

  • MiR-124 shows potential as a predictive biomarker for HBV-ACLF prognosis.
  • MiR-124 may serve as a therapeutic target for mitigating severe liver injury associated with cytokine storms in HBV-ACLF.
Keywords:
Hepatitis B virusIL-6Kupffer cellsLiver injurymicroRNA-124

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