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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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8,11,14-Eicosatrienoic Acid / analogs & derivatives*
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8,11,14-Eicosatrienoic Acid / urine
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Animals
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Arachidonic Acid / blood
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Arachidonic Acid / urine
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Cell Line
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Cytochrome P-450 CYP2J2
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Cytochrome P-450 Enzyme System / blood
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism*
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Cytochrome P-450 Enzyme System / urine
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Diabetes Mellitus, Experimental / blood*
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / physiopathology
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Diabetes Mellitus, Experimental / urine
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Diabetic Nephropathies / blood*
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Diabetic Nephropathies / chemically induced
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Diabetic Nephropathies / complications
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Diabetic Nephropathies / physiopathology
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Diabetic Nephropathies / urine
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Epithelial-Mesenchymal Transition / drug effects
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Gene Expression / drug effects
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Kidney / drug effects
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Kidney / metabolism*
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Kidney / physiopathology
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Kidney Function Tests
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Mice
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Mice, Transgenic
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Signal Transduction*
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Smad Proteins / blood
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Smad Proteins / genetics
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Smad Proteins / urine
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Streptozocin / administration & dosage
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Streptozocin / adverse effects
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Transforming Growth Factor beta1 / pharmacology*
Substances
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Smad Proteins
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Transforming Growth Factor beta1
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Arachidonic Acid
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11,12-epoxy-5,8,14-eicosatrienoic acid
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Streptozocin
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Cytochrome P-450 Enzyme System
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Cytochrome P-450 CYP2J2
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8,11,14-Eicosatrienoic Acid