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.
Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):63-71. doi: 10.1016/j.prostaglandins.2011.06.009. Epub 2011 Jun 30.
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.
细胞色素 P450（CYP）环氧合酶将花生四烯酸代谢为环氧化物二十碳三烯酸（EETs），在心血管系统中发挥着重要而多样的作用。EETs 在心血管系统中的抗炎、抗细胞凋亡、促血管生成和抗高血压特性表明 EETs 在糖尿病肾病中具有有益作用。本研究探讨了内皮细胞特异性过表达 CYP2J2 环氧合酶对链脲佐菌素诱导的糖尿病小鼠糖尿病肾病的影响。内皮细胞 CYP2J2 过表达可减轻尿微量白蛋白和肾小球硬化所衡量的肾脏损伤。这些作用与肾脏中 TGF-β/Smad 信号的抑制有关。事实上，CYP2J2 的过表达可防止 TGF-β1 诱导的体外肾小管上皮-间充质转化。这些发现强调了 CYP 环氧合酶-EET 系统在糖尿病肾病发病机制中的有益作用。
