The Gp130/STAT3-endoplasmic Reticulum Stress Axis Regulates Hepatocyte Necroptosis in Acute Liver Injury

Overview

Journal Croat Med J

Specialty General Medicine

Date 2023 Jul 1

PMID 37391912

Authors

Xia Li

Jie Wang

Ying Li

Wei He

Qi-Jiao Cheng

Xia Liu

De-Lin Xu

Zhi-Gang Jiang

Xue Xiao

Yi-Huai He

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate the effect of the gp130/STAT3-endoplasmic reticulum (ER) stress axis on hepatocyte necroptosis during acute liver injury.

Methods: ER stress and liver injury in LO2 cells were induced with thapsigargin, and in BALB/c mice with tunicamycin and carbon tetrachloride (CCl4). Glycoprotein 130 (gp130) expression, the degrees of ER stress, and hepatocyte necroptosis were assessed.

Results: ER stress significantly upregulated gp130 expression in LO2 cells and mouse livers. The silencing of activating transcription factor 6 (ATF6), but not of ATF4, increased hepatocyte necroptosis and mitigated gp130 expression in LO2 cells and mice. Gp130 silencing reduced the phosphorylation of CCl4-induced signal transducer and activator of transcription 3 (STAT3), and aggravated ER stress, necroptosis, and liver injury in mice.

Conclusion: ATF6/gp130/STAT3 signaling attenuates necroptosis in hepatocytes through the negative regulation of ER stress during liver injury. Hepatocyte ATF6/gp130/STAT3 signaling may be used as a therapeutic target in acute liver injury.

Citing Articles

Mangiferin Ameliorates CCl-Triggered Acute Liver Injury by Inhibiting Inflammatory Response and Oxidative Stress: Involving the Nrf2-ARE Pathway.

Shi C, Li Y, You Z, Tian Y, Zhu X, Xu H J Inflamm Res. 2024; 17:7081-7097.

PMID: 39380664 PMC: 11460351. DOI: 10.2147/JIR.S476288.

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