Original scientific paper
https://doi.org/10.3325/cmj.2023.64.149
The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury
Xia Li
; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Jie Wang
; Department of General Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Ying Li
; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Wei He
; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Qi-Jiao Cheng
; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Xia Liu
; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
De-Lin Xu
; Department of Cell Biology, Zunyi Medical University, Zunyi, Guizhou, China
Zhi-Gang Jiang
; School of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
Xue Xiao
; Department of General Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Xue Xiao
; Department of General Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
Yi-Huai He
; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
*
* Corresponding author.
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
Keywords
Hrčak ID:
331524
URI
Publication date:
30.6.2023.
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