9-cis-retinoic Acid Alleviates Cholestatic Liver Injury By Elevating MRP3 Expression By Inhibiting The Sumoylation Of RXRα

Objective: Vitamin A and it’s metabolites were found to be protective for the cholestatic liver injury,but the exact machanisms of them in cholestatic liver injury remain unclear.The objective of this study was to determine the function and mechanisms of 9-cis-retinoic acid,the metabolite of vitamin A in cholestatic liver injury.Design: The effects of 9-cis-retinoic acid on hepatocytes stimulated by bile acid were explored at the cellular level.The BDL-mice were treated with 9-cis-retinoic acid through the tail intravenous injection for 10 days.The liver function and histology were assessed in matched group and experimental group.The expression of MRP3 in the liver tissue was tested by qRT-PCR,western blotting and IHC.Effect of RXRα sumoylation on MRP3 expreesion was explored in cellular level.Influence of 9-cis-retinoic acid on RXRα sumoylation was also tested in cellular level.Results : 9-cis-retinoic acid decreases the serum ALT and AST level,alleviates hepatic necrosis of the BDL-mice and reduces the toxicity of bile acid to the hepatocyte.9-cis-retinoic acid weaken the sumoylation of RXRα and elevates MRP3 expression.Inhibition of RXRα sumoylation lighten the interaction of RXRα and RARa,which increases the MRP3 expression.Conclusions: 9-cis-retinoic acid alleviates cholestatic liver injury by elevating MRP3 expression by inhibiting the sumoylation of RXRα.