4.7 Article

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

Journal

ANTIVIRAL RESEARCH
Volume 211, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.antiviral.2022.105510

Keywords

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

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This study reveals that serum miR-124 can serve as a compensatory predictive factor for organ failure and the 28-day prognosis in patients with HBV-ACLF. Moreover, miR-124 overexpression can decrease IL-6 secretion and relieve liver necrosis by targeting the 3′-untranslated region of STAT3 and inhibiting IL-6/STAT3 signaling. These findings suggest that miR-124 may have potential as a biomarker and therapeutic target for severe liver injury.
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 inflam-mation 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 & PRIME;-untranslated region of signal transducer and activator of transcription 3 (STAT3) and inhibits IL-6/STAT3 signaling, which reduces pro-inflammatory Kupffer cell po-larization. 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.

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