Role of GSK-3β in Renalase inhibition of renal fibrosis
Objective To explore the role of glycogen synthase kinase-3 β(GSK-3 β)in Renalase's anti-renal fi-brosis process and its possible mechanism.Methods C57BL/6 mice were divided into(1)Sham+Ad-β-gal,(2)Sham+Ad-Renalase,(3)UUO+Ad-β-gal,(4)UUO+Ad-Renalas groups to observe the change of GSK-3β expression.Among them,UUO group was a model group of renal fibrosis caused by unilateral ureteral liga-tion,Sham group was a sham operation control group,Ad-Renalase was an over-expressed Renalase adenovirus,and Ad-β-gal was a control adenovirus.After overexpressing(UUO+Ad-Renalase+AAV-GSK-3 β)or knocking down(UUO+Ad-Renalase+Ad-GSK-3β-RNAi)GSK-3β by virus transfection.Results Compared with Sham group,the expression of GSK-3[3 in UUO group was significantly increased.Compared with UUO+Ad-β-gal group,the deposition of fiber tissue decreased,the expression of Col-Ⅰ,fibronectin(FN)and GSK-3β was down-regulated in UUO+Ad-Renalase group.After overexpression of GSK-3 β,the anti-fibrosis effect of Rena-lase was counteracted,but when GSK-3β was knocked down,compared with UUO+Ad-Renalase group,the fi-brosis did not further improve in UUO+Ad-Renalase+Ad-GSK-3β-RNAi group.Meanwhile,compared with Sham group,endoplasmic reticulum stress in UUO group was obviously activated,and the activated endoplasmic reticulum stress was obviously inhibited after overexpression of Renalase.When endoplasmic reticulum stress ago-nist was added,the anti-fibrosis effect of Renalase was obviously weakened in UUO+Ad-Renalase+TM group compared with UUO+Ad-Renalase group,and down-regulated GSK-3β was obviously recovered.However,the expression of endoplasmic reticulum stress markers did not change significantly whether GSK-3β was overex-pressed or knocked down.Conclusion The study confirmed that Renalase can reduce the expression of GSK-3βby inhibiting endoplasmic reticulum stress,thus delaying renal fibrosis inUUO.
国家科技期刊平台
NSTL
万方数据
维普
