Oncotarget

Research Papers:

SIRT3-KLF15 signaling ameliorates kidney injury induced by hypertension

Na Li _, Jie Zhang, Xuefang Yan, Chen Zhang, Hui Liu, Xiaolan Shan, Jingyuan Li, Yi Yang, Chengmin Huang, Peng Zhang, Yun Zhang and Peili Bu

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Oncotarget. 2017; 8:39592-39604. https://doi.org/10.18632/oncotarget.17165

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Abstract

Na Li1, Jie Zhang1, Xuefang Yan1, Chen Zhang1, Hui Liu1, Xiaolan Shan1, Jingyuan Li1, Yi Yang1, Chengmin Huang1, Peng Zhang1, Yun Zhang1 and Peili Bu1

1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China

Correspondence to:

Peili Bu, email: bupeili@outlook.com

Keywords: SIRT3, KLF15, honokiol, hypertensive kidney injury, podocyte

Received: October 15, 2016     Accepted: March 27, 2017     Published: April 17, 2017

ABSTRACT

Renal fibrosis participates in the progression of hypertension-induced kidney injury. The effect of SIRT3, a member of the NAD+-dependent deacetylase family, in hypertensive nephropathy remains unclear. In this study, we found that SIRT3 was reduced after angiotensin II (AngII) treatment both in vivo and in vitro. Furthermore, SIRT3-knockout mice aggravated hypertension-induced renal dysfunction and renal fibrosis via chronic AngII infusion (2000 ng/kg per minute for 42 days). On the contrary, SIRT3-overexpression mice attenuated AngII-induced kidney injury compared with wild-type mice. Remarkably, a co-localization of SIRT3 and KLF15, a kidney-enriched nuclear transcription factor, led to SIRT3 directly deacetylating KLF15, followed by decreased expression of fibronectin and collagen type IV in cultured MPC-5 podocytes. In addition, honokiol (HKL), a major bioactive compound isolated from Magnolia officinalis (Houpo), suppressed AngII-induced renal fibrosis through activating SIRT3-KLF15 signaling. Taken together, our findings implicate that a novel SIRT3-KLF15 signaling may prevent kidney injury from hypertension and HKL can act as a SIRT3-KLF15 signaling activator to protect against hypertensive nephropathy.


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