首页 / 院系成果 / 成果详情页

SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy 期刊论文

编号：

1896ff29-4313-42b9-b2a9-862ec35dd462
作者：

Zhang, Huan(张环)#^[1]Liu, Xiuxia^[2];Zhou, Shanshan(周珊珊)^[3]Jia, Ye(贾冶)^[4]Li, Ying^[5];Song, Yuguo^[6,7];Wang, Junnan(王珺楠)*^[8]Wu, Hao(吴昊)*^[9,10]
语种：

英文
期刊：

JOURNAL OF MOLECULAR ENDOCRINOLOGY ISSN：0952-5041 2018 年 60 卷 2 期 (145 - 157) ; FEB
收录：
关键词：

antioxidant diabetic nephropathy KEAP1 JNK NRF2
摘要：

c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125' s protection against DN. To test the role of NRF2 in SP600125' s effect, streptozotocin-induced C57BL/6 wild-type (WT) and Nrf2-knockout (KO) diabetic mice were treated in the presence or absence of SP600125, for 24 weeks. To explore the mechanism by which SP600125 activates NRF2, mouse mesangial cells (MMCs) were treated with high glucose (HG), in the presence or absence of either SP600125 or JNK siRNA. SP600125 significantly attenuated the diabetes-induced renal oxidative stress, inflammation, fibrosis, pathological change and dysfunction in the WT, but not the Nrf2 KO mice. SP600125 inactivated JNK, inhibited kelch-like ECH-associated protein 1 expression, preserved NRF2 protein and facilitated its nuclear translocation in the kidneys of the WT mice, the effects of which were similarly produced by either SP600125 or JNK siRNA in HG-treated MMCs. Further, both SP600125 and JNK siRNA alleviated HG-induced mesangial oxidative stress and expression of inflammatory and fibrotic genes. The present study demonstrates that NRF2 is required for SP600125' s protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression.
推荐引用方式
GB/T 7714：

Zhang Huan,Liu Xiuxia,Zhou Shanshan, et al. SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy [J].JOURNAL OF MOLECULAR ENDOCRINOLOGY,2018,60(2):145-157.
APA：

Zhang Huan,Liu Xiuxia,Zhou Shanshan,Jia Ye,&Wu Hao.(2018).SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy .JOURNAL OF MOLECULAR ENDOCRINOLOGY,60(2):145-157.
MLA：

Zhang Huan, et al. "SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy" .JOURNAL OF MOLECULAR ENDOCRINOLOGY 60,2(2018):145-157.
条目包含文件：

文件类型：PDF,文件大小：

正在加载全文

未找到全文

浏览次数：14  下载次数：0

分享到：

浏览次数：14

下载次数：0

打印次数：0