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MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease 期刊论文

编号：

c285a552-47af-48df-a35b-533d6dc2463d
作者：

Guo, Weiying(郭蔚莹)#^[1]Tian, Dan^[2];Jia, Ye(贾冶)^[3]Huang, Wenlin^[4];Jiang, Mengnan^[5];Wang, Junnan^[6];Sun, Weixia(孙伟霞)*^[3]Wu, Hao(吴昊)*^[7,8]
语种：

英文
期刊：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH ISSN：0167-4889 2018 年 1865 卷 8 期 (1034 - 1045) ; AUG
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关键词：

Diabetes Diabetic nephropathy Nrf2 Oxidative stress P53
摘要：

Oxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hypothesized that MDM2 enhances NRF2 antioxidant signaling in DKD given that MDM2 is a key negative regulator of P53. The MDM2 inhibitor nutlin3a elevated renal P53, inhibited NRF2 signaling and induced oxidative stress, inflammation, fibrosis, DKD-like renal pathology and albuminuria in the wild-type (WT) non-diabetic mice. These effects exhibited more prominently in nutlin3a-treated WT diabetic mice. Interestingly, nutlin3a failed to induce greater renal injuries in the Nrf2 knockout (KO) mice under both the diabetic and non-diabetic conditions, indicating that NRF2 predominantly mediates MDM2's action. On the contrary, P53 inhibition by pifithrin-a activated renal NRF2 signaling and the expression of Mdm2, and attenuated DKD in the WT diabetic mice, but not in the Nrf2 KO diabetic mice. In high glucose-treated mouse mesangial cells, P53 gene silencing completely abolished nutlin3a's inhibitory effect on NRF2 signaling. The present study demonstrates for the first time that MDM2 controls renal NRF2 antioxidant activity in DKD via inhibition of P53, providing MDM2 activation and P53 inhibition as novel strategies in the management of DKD.
推荐引用方式
GB/T 7714：

Guo Weiying,Tian Dan,Jia Ye, et al. MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease [J].BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2018,1865(8):1034-1045.
APA：

Guo Weiying,Tian Dan,Jia Ye,Huang Wenlin,&Wu Hao.(2018).MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease .BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,1865(8):1034-1045.
MLA：

Guo Weiying, et al. "MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease" .BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1865,8(2018):1034-1045.
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