Fyn deficiency inhibits oxidative stress by decreasing c-Cbl-mediated ubiquitination of Sirt1 to attenuate diabetic renal fibrosis

Shanshan Li,Zeyuan Lin,Haiming Xiao,Zhanchi Xu,Chuting Li,Jingran Zeng,Xi Xie,Li Deng,Heqing Huang

Metabolism（2023）

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摘要

•This study reported the role of Fyn in diabetic nephropathy (DN).•We proposed Fyn as a potential therapeutic target against DN.•Fyn deficiency exerted antioxidant effects by activating the Sirt1/Foxo3a pathway.•Fyn facilitated the bond of c-Cbl and Sirt1 by phosphorylation at Tyr731 of c-Cbl.•c-Cbl promoted K48-linked polyubiquitination at Lys377 and Lys513 of Sirt1.

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24 h UP,BUN,CHX,Cr,DHE,DN,ECM,FBG,FN,GMCs,GSP,HE,HEK,HG,ICAM-1,IF,IHC,IP,KW/BW,LPO,MDA,NAC,NC,NG,OS,PAS,ROS,SD,Si-RNA,SOD,SPF

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