Oncotarget

Research Papers:

Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy

Li He, Ying Fan, Wenzhen Xiao, Teng Chen, Jiejun Wen, Yang Dong, Yiyun Wang, Shiqi Li, Rui Xue, Liyang Zheng, John Cijiang He and Niansong Wang _

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Oncotarget. 2017; 8:111295-111308. https://doi.org/10.18632/oncotarget.22784

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Abstract

Li He1,*, Ying Fan1,*, Wenzhen Xiao1,2, Teng Chen1, Jiejun Wen1, Yang Dong1, Yiyun Wang1, Shiqi Li1, Rui Xue1, Liyang Zheng1, John Cijiang He2 and Niansong Wang1

1Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

2Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

*These authors have contributed equally to this work

Correspondence to:

Niansong Wang, email: wangniansong2012@163.com

John Cijiang He, email: cijiang.he@mssm.edu

Ying Fan, email: fanyingsh@126.com

Keywords: hyperuricemic nephropathy; hyperuricemia; ER stress; renal tubular cells; Febuxostat

Received: June 16, 2017     Accepted: November 16, 2017     Published: November 30, 2017

ABSTRACT

Hyperuricemia contributes to kidney tubular injury and kidney fibrosis. However, the underlying mechanism remains unclear. Here we examined the role of RTN1A, a novel endoplasmic reticulum (ER)-associated protein and ER stress in hyperuricemic nephropathy. We first found the expression of RTN1A and ER stress markers was significantly increased in kidney biopsies of hyperuricemia patients with kidney injury. In a rat model of hyperuricemic nephropathy (HN) established by oral administration of a mixture of adenine and potassium oxonate, increased expression of RTN1A and ER stress was shown in tubular and interstitial compartment of rat kidneys. Treatment of Febuxostat, a new selective inhibitor of xanthine oxidase (XO), not only attenuated renal tubular injury and tubulointerstitial fibrosis, but also reduced uric acid crystals deposition in HN rat kidneys. In vitro, Febuxostat also reduced ER stress and apoptosis in uric acid treated tubular epithelial cells. Our data suggest that RTN1A and ER stress mediate tubular cell injury and kidney fibrosis in HN. Urate-lowering therapy (ULT) with Febuxostat attenuates uric-acid induced ER stress in renal tubular cells and the progression of HN.


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