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

Jinyu Wang; Xueyun Zhang; Jiajia Han; Pu Zhou; Xueping Yu; Zhongliang Shen; Richeng Mao; Mengji Lu; Yuxian Huang; Jiming Zhang

doi:10.1016/j.antiviral.2022.105510

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

Antiviral Res. 2023 Mar:211:105510. doi: 10.1016/j.antiviral.2022.105510. Epub 2022 Dec 26.

Authors

Affiliations

¹ Department 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.
² Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Germany.
³ Department 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; Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
⁴ Department 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; Department of Infectious Diseases, Jing'An Branch of Huashan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Infectious Diseases and Biosecurity, Key Laboratory of Medical Molecular Virology of the Ministry of Education and Ministry of Health (MOH&MOE), Fudan University, Shanghai, China. Electronic address: jmzhang@fudan.edu.cn.

PMID: 36581048
DOI: 10.1016/j.antiviral.2022.105510

Abstract

MicroRNA-124 (miR-124) is related to liver injury due to chronic hepatitis B (CHB) and hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, the mechanism whereby miR-124 regulates liver inflammation remains unknown. In this study, we show that serum miR-124 serves as a compensatory predictive factor for organ failure and the 28-day prognosis of patients with HBV-ACLF. Moreover, within a mouse model of concanavalin A-induced acute liver injury, miR-124 is highly expressed in Kupffer cells. Overexpression of miR-124 significantly decreases interleukin-6 (IL-6) secretion, and relieves pathological liver necrosis to a great extent. Mechanistically, miR-124 directly targets the 3'-untranslated region of signal transducer and activator of transcription 3 (STAT3) and inhibits IL-6/STAT3 signaling, which reduces pro-inflammatory Kupffer cell polarization. Collectively, our findings suggest that miR-124 can potentially serve as a predictive biomarker for HBV-ACLF prognosis and may represent a promising therapeutic target for relieving severe liver injury resulting from cytokine storms.

Keywords: Hepatitis B virus; IL-6; Kupffer cells; Liver injury; microRNA-124.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hepatitis B virus / metabolism
Hepatitis B, Chronic*
Interleukin-6 / metabolism
Kupffer Cells / metabolism
Kupffer Cells / pathology
Liver / pathology
Mice
MicroRNAs*
STAT3 Transcription Factor / metabolism

Substances

Interleukin-6
STAT3 Transcription Factor
MicroRNAs