Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice

被引：33

作者：

Chen, Guangzhi ^{[1
,2
]}

Wang, Peihua ^{[1
,2
]}

Zhao, Gang ^{[1
,2
]}

Xu, Gang ^{[1
,2
]}

Gruzdev, Artiom ^{[3
]}

Zeldin, Darryl C. ^{[3
]}

Wang, Dao Wen ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Gene Therapy Ctr, Wuhan 430030, Peoples R China

[3] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA

来源：

PROSTAGLANDINS & OTHER LIPID MEDIATORS | 2011年 / 96卷 / 1-4期

关键词：

Arachidonic acids; Cytochrome P450 epoxygenase; Streptozotocin; Diabetic nephropathy; Tubular epithelial-inesenchymal; transdifferentiation; GROWTH-FACTOR-BETA; SOLUBLE EPOXIDE HYDROLASE; EPITHELIAL-MYOFIBROBLAST TRANSDIFFERENTIATION; ACTIVATED PROTEIN-KINASE; PROXIMAL TUBULAR CELLS; EPOXYEICOSATRIENOIC ACIDS; TGF-BETA; MESENCHYMAL TRANSITION; SIGNALING PATHWAYS; TUBULOINTERSTITIAL FIBROSIS;

D O I：

10.1016/j.prostaglandins.2011.06.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs). which play important and diverse roles in the cardiovascular system. The anti-inflammatory, antiapoptotic, pro-angiogenic, and anti-hypertensive properties of EETs in the cardiovascular system suggest a beneficial role for EETs in diabetic nephropathy. This study investigated the effects of endothelial specific overexpression of CYP2J2 epoxygenase on diabetic nephropathy in streptozotocin-induced diabetic mice. Endothelial CYP2J2 overexpression attenuated renal damage as measured by urinary microalbumin and glomerulosclerosis. These effects were associated with inhibition of TGF-beta/Smad signaling in the kidney. Indeed, overexpression of CYP2J2 prevented TGF-beta 1-induced renal tubular epithelial-mesenchymal transition in vitro. These findings highlight the beneficial roles of the CYP epoxygenase-EET system in the pathogenesis of diabetic nephropathy. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：63 / 71

页数：9

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