细胞色素 P450 环氧合酶 CYP2J2 可减轻链脲佐菌素诱导的糖尿病小鼠的肾病。
Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice.
机构信息
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.
出版信息
Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):63-71. doi: 10.1016/j.prostaglandins.2011.06.009. Epub 2011 Jun 30.
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.
摘要
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。
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本文引用的文献
1
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Nat Rev Nephrol. 2011 Jan;7(1):36-44. doi: 10.1038/nrneph.2010.152. Epub 2010 Nov 2.
2
Cytochrome P450 2J2 is highly expressed in hematologic malignant diseases and promotes tumor cell growth.细胞色素 P450 2J2 在血液恶性肿瘤中高度表达，并促进肿瘤细胞生长。
J Pharmacol Exp Ther. 2011 Feb;336(2):344-55. doi: 10.1124/jpet.110.174805. Epub 2010 Oct 28.
3
Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice.人细胞色素 P450 加单氧酶环氧合酶的内皮表达降低血压并减轻小鼠高血压引起的肾脏损伤。
FASEB J. 2010 Oct;24(10):3770-81. doi: 10.1096/fj.10-160119. Epub 2010 May 21.
4
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Acta Pharmacol Sin. 2010 Feb;31(2):211-8. doi: 10.1038/aps.2009.184.
5
Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice.CYP2J3 表达增加可减轻果糖处理大鼠和 db/db 小鼠的胰岛素抵抗。
Diabetes. 2010 Apr;59(4):997-1005. doi: 10.2337/db09-1241. Epub 2010 Jan 12.
6
Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y) (Akita) mice.Ins2(+/C96Y) (Akita) 小鼠遗传背景对白蛋白尿和肾脏损伤的影响。
Am J Physiol Renal Physiol. 2010 Mar;298(3):F788-95. doi: 10.1152/ajprenal.90515.2008. Epub 2009 Dec 30.
7
TGF-beta and fibrosis in different organs - molecular pathway imprints.不同器官中的转化生长因子-β与纤维化——分子途径印记
Biochim Biophys Acta. 2009 Aug;1792(8):746-56. doi: 10.1016/j.bbadis.2009.06.004. Epub 2009 Jun 17.
8
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Nephrology (Carlton). 2009 Apr;14(3):311-20. doi: 10.1111/j.1440-1797.2008.01059.x. Epub 2009 Mar 10.
9
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Am J Physiol Renal Physiol. 2009 Mar;296(3):F614-21. doi: 10.1152/ajprenal.90500.2008. Epub 2008 Dec 17.
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