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Mol Cell Endocrinol. 2018 Jan 15;460:1-13. doi: 10.1016/j.mce.2017.04.027. Epub 2017 Jun 1.

SIRT3 prevents angiotensin II-induced renal tubular epithelial-mesenchymal transition by ameliorating oxidative stress and mitochondrial dysfunction.

Author information

1
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China.
2
Research & Development Center, Infinitus (China) Company Ltd., Guangzhou, People's Republic of China.
3
Department of Pharmacology, School of Medicine, Jishou University, Jishou 416000, Hunan Province, People's Republic of China.
4
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China. Electronic address: chshaor@mail.sysu.edu.cn.
5
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China; National and Local Joint Engineering Laboratory of Druggabilitiy Assessment and Evaluation, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China. Electronic address: liupq@mail.sysu.edu.cn.

Abstract

Silent mating type information regulation 2 homolog 3 (SIRT3) is a major protective mediator that ameliorates oxidative stress and mitochondrial dysfunction, which are associated with the pathogenesis of epithelial-mesenchymal transition (EMT). The present study was aimed to investigate the potential role of SIRT3 in renal tubular EMT both in vitro and in vivo. Firstly, we showed that the expression of SIRT3 was repressed in angiotensin II-induced EMT. SIRT3 deficiency triggered EMT response, while over-expression of SIRT3 attenuated EMT response. In addition, over-expression of SIRT3 repressed AngⅡ-induced excessive production of mitochondrial superoxide, as well as mitochondrial dysfunction evidenced by the maintenance of mitochondrial number and morphology, and the stabilization of mitochondrial membrane potential. In conclusion, these findings identify a protective role of SIRT3 against angiotensin II-induced EMT in the kidney, and suggest SIRT3 upregulation is a potential therapeutic strategy for the treatment of renal tubulointerstitial fibrosis.

KEYWORDS:

Angiotensin II; Mitochondrial dysfunction; MnSOD; Oxidative stress; Renal tubular EMT; SIRT3

PMID:
28579116
DOI:
10.1016/j.mce.2017.04.027
[Indexed for MEDLINE]

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