遵义医科大学学报2024，Vol.47Issue(1)：1-9,9.
基于糖原合成酶激酶-3β及内质网应激探讨Renalase抗肾脏纤维化的作用机制
Role of GSK-3β in Renalase inhibition of renal fibrosis
摘要
Abstract
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.关键词
糖原合成酶激酶-3β/肾脏纤维化/Renalase/内质网应激Key words
glycogen synthase kinase-3β/renal fibrosis/renalase/endoplasmic reticulum stress分类
医药卫生引用本文复制引用
吴逸如,白雨,张启东,刘文虎..基于糖原合成酶激酶-3β及内质网应激探讨Renalase抗肾脏纤维化的作用机制[J].遵义医科大学学报,2024,47(1):1-9,9.基金项目
国家自然科学基金资助项目(NO:82000700) （NO:82000700）
北京市优秀人才(NO:2018000021469G201). （NO:2018000021469G201）
