title: Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice.
abstract: Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. The anti-inflammatory, anti-apoptotic, 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-β/Smad signaling in the kidney. Indeed, overexpression of CYP2J2 prevented TGF-β1-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.
authors: Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave., Wuhan 430030, People's Republic of China.
authors: Guangzhi
authors: G
authors: Chen
authors: Peihua
authors: P
authors: Wang
authors: Gang
authors: G
authors: Zhao
authors: Gang
authors: G
authors: Xu
authors: Artiom
authors: A
authors: Gruzdev
authors: Darryl C
authors: DC
authors: Zeldin
authors: Dao Wen
authors: DW
authors: Wang
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000652:urine; D002460:Cell Line; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood* / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology / Q000652:urine; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007677:Kidney Function Tests; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D051785:Smad Proteins / Q000097:blood / Q000235:genetics / Q000652:urine; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D016718:Arachidonic Acid; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid