Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgf beta 1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice

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	Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgf beta 1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice
	Wei, Jie ; Zhang, Ye ; Luo, Yu ; Wang, Zhen ; Bi, Shulin ; Song, Dan ; Dai, Yuan ; Wang, Tao ; Qiu, Longxin ; Wen, Longping ; Yuan, Li ; Yang, James Y. ; Wei J(魏杰) ; Wang T(王涛) ; Yuan L(袁立) ; Yang CY(杨朝勇)
刊名	http://dx.doi.org/10.1016/j.freeradbiomed.2013.10.811
	2014
关键词	INDUCED OXIDATIVE STRESS ALPHA-LIPOIC ACID MESENCHYMAL TRANSITION ANTIOXIDATIVE DEFENSE TARGETING ZEB1 MIR-200 FAMILY CANCER CELLS E-CADHERIN NEPHROPATHY PATHWAY
英文摘要	973 Program of China [2009CB941601]; National Science Foundation of China [31271239]; Fujian Provincial Department of Science and Technology [2010L0002]; 111 Project of Education of China [B06018]; Open Research Fund of the State Key Laboratory of Cellular Stress Biology, Xiamen University [SKLCSB2012KF005]; China Postdoctoral Foundation [2012M511446]; Aberrant regulation in oxidative stress, fibrogenesis, and the epithelial-mesenchymal transition (EMT) in renal cells under hyperglycemic conditions contributes significantly to the onset and progression of diabetic nephropathy. The mechanisms underlying these hyperglycemia-induced dysregulations, however, have not been dearly elucidated. Herein, we report that aldose reductase is capable of regulating the expression of miR-200a-3p/141-3p negatively in renal mesangial cells. MiR-200a-3p/141-3p, in turn, act to target Keap1, Tgf beta 2, fibronectin, and Zeb2 directly and regulate Tgf beta 1 and Nrf2 indirectly under high-glucose conditions, resulting in profound dysregulations in Keap1-Nrf2, Tgf beta 1/2, and Zeb1/2 signaling. In vivo in streptozotocin-induced diabetic mice, we found that aldose reductase deficiency caused significant elevations in miR-200a-3p/141-3p in the renal cortex, which were accompanied by a significant downregulation of Keap1, Tgf beta 1/2, and fibronectin but significant upregulation of Nrf2. Moreover, in vivo administration of inhibitors of miR-200a-3p in diabetic animals significantly exacerbated cortical and glomerular fibrogenesis and increased urinary albumin excretion, tightly linking dysregulated miR-200a-3p with the development of diabetic nephropathy. Collectively, our results reveal a novel mechanism whereby hyperglycemia induces aldose reductase to regulate renal expression of miR-200a-3p/141-3p to coordinately control hyperglycemia-induced renal oxidative stress, fibrogenesis, and the EMT. Our novel findings also suggest that inhibition of aldose reductase and in vivo renal cortical restoration of miR-200a-3p/141-3p or their combination are very promising avenues for the development of therapeutic strategies or drugs against diabetic nephropathy. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
语种	英语
出版者	ELSEVIER SCIENCE INC
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90834]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Wei, Jie,Zhang, Ye,Luo, Yu,et al. Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgf beta 1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice[J]. http://dx.doi.org/10.1016/j.freeradbiomed.2013.10.811,2014.
APA	Wei, Jie.,Zhang, Ye.,Luo, Yu.,Wang, Zhen.,Bi, Shulin.,...&杨朝勇.(2014).Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgf beta 1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice.http://dx.doi.org/10.1016/j.freeradbiomed.2013.10.811.
MLA	Wei, Jie,et al."Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgf beta 1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice".http://dx.doi.org/10.1016/j.freeradbiomed.2013.10.811 (2014).