MYCT1 Attenuates Renal Fibrosis and Tubular Injury in Diabetic Kidney Disease

Overview

Journal iScience

Publisher Cell Press

Date 2023 Sep 4

PMID 37664593

Authors

Xin Li

Qiu-Ling Fan

Tian-Kui Ma

Cong Liu

Hang Shi

Yuan-Yuan Sun

Yue Wang

Dong-Xue Ding

Ao Tang

Yu Qin

Qi Yang

Hong Ding

Hang-Yu Li

Wei-Neng Fu

Affiliations

Soon will be listed here.

Abstract

Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in and DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-β1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-β1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

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