The Mechanism And Significance Of Endoplasmic Reticulum Stress Up-regulating The Expression Of Gp130 Protein In The Liver Of Acute Liver Injury

Objective:The aim of this study was to investigate the mechanism and significance of ERS up-regulating intrahepatic gp130 expression in acute liver injury.Methods:（1）In LO2 cells,knockdown of ATF6 reduced TG-induced gp130 protein level（P<0.01）,while ATF4 knockdown did not affect TG-induced changes in gp130 protein level（P>0.05）;（2）CCl₄In the induced model mice,the knockdown of ATF6 not only significantly reduced the protein level of gp130,but also aggravated the liver injury（P<0.01）;（3）The p-STAT3 protein level was down-regulated after the specific gp130expression in the liver was down-regulated（P<0.01）,and CCl₄-induced liver injury,hepatocyte programmed necrosis and ERS were aggravated（P<0.01）.Results:（1）In LO2 cells,knockdown of ATF6 reduced TG-induced gp130 protein levels,while ATF4 knockdown did not affect TG-induced changes in gp130 protein levels;（2）CCl₄-induced model mice,knockdown of ATF6 Not only significantly reduced gp130protein level,but also aggravated liver injury;（3）Down-regulation of intrahepatic-specific gp130 aggravated CCl₄-induced ERS,hepatocyte programmed necrosis and liver injury.Conclusion:In acute liver injury,ERS up-regulates the expression of gp130 in hepatocytes by activating ATF6 signaling;the up-regulated gp130 attenuates the programmed necrosis of hepatocytes in liver injury,and the mechanism may be to negatively regulate ERS by increasing the activity level of STAT3 signaling.