The Effect And Underlying Mechanism Of PP2Ac? In The Process Of Acute Liver Injury

Aims:In this study,the expression and effect of PP2Aca in the process of acute liver injury was detected.Furthermore,we explored the role of PP2Aca in liver fibrogenesis and its underlying mechanism.Methods:1.The liver tissues of subacute liver injury patients were immunostained with anti-PP2Aca antibody.2.Liver PP2Aca mRNA expression and protein level were detected in the CCl4-induced acute liver injury mice.3.We investigated the role of PP2Aca in CCl4-induced acute liver injury model with hepatocyte-specific PP2Aca knockout mice.4.The role of PP2Aca in liver fibrogenesis was confirmed by Masson staining,anti-collagen1,anti-?-SMA immunohistochemistry.5.We established CCl4-induced acute liver injury and fibrogenesis in vitro model to explore the underlying mechanism how PP2Aca regulates liver fibrogenesis.6.ChIP and dual luciferase assay were used to ascertain whether NF-?B regulates plasminogen expression direactly.Results:1.Higher expression of PP2Aca was detected in the liver tissues of subacute liver injury compared to control.2.We detected higher PP2Aca mRNA and protein level in the CCl4-induced acute liver injury mice.3.We detected less hepatic necrosis and lower serum ALT and AST in hepatocyte-specific PP2Aca knockout mice after CCl4 injection.4.Liver deficiency of PP2Aca decreased the serum TGF-? level and hepatic collagen accumulation in CCl4-induced acute liver injury.5.Inhibition of PP2Aca increased plasminogen expression in CCl4-treated LO-2 cell.6.Plasmin mitigated the activation of LX-2 cell via downregulating TGF-? level.7.NF-?B activated plasminogen transcription by binding directly to the plasminogen promoter.Conclusion:1.Liver PP2Aca expression was upregulated in acute liver injury.2.Liver deficiency of PP2Aca protected the liver from acute injury.3.Liver deficiency of PP2Aca alleviated liver fibrogenesis in acute liver injury.4.Inhibition of PP2Aca increased plasminogen expression via regulating NF-?B pathway,consequently alleviated liver fibrogenesis.