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Published on: November 27, 2019
The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury
1Yi-Huai He, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, No. 201 Dalian Street, Zunyi, 563000, Guizhou, China, 993565989@qq.com.
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.
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