Development of CYP2J2 gene therapy for glomeruonephritis and diabetic nephropathy

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CYP2J2 is a crucial regulator of epoxyeicosatrienoic acid production from arachidonic acid. Epoxyeicosatrienoic acid is a vasodilator that relaxes vascular smooth muscle cells and has anti-inflammatory properties against vascular cells. Therefore, it is indicated that induction of CYP2J2 gene in mesangial cells and endothelial cells shows protective effects against kidney by the improvement of blood flow and anti-inflammatory effects.We studied the effects of angiotensin II, that promotes oxidative stress and inflammation in vascular cells, on CYP2J2 gene expression. We demonstrated increased CYP2J2 mRNA expression in cultured endothelial cells and mesangial cells by RT-PCR. Tumor necrosis factor-a that is an inflammatory cytokine showed similar effects on CYP2J2 mRNA expression in cultured endothelial cells and mesangial cells. These data suggest that inflammatory stimuli increase CYP2J2 mRNA expression in endothelial cells and mesangial cells.Also, we demonstrated that tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression is decreased by overexpression of CYP2J2 in cultured endothelial cells. This result indicates that CYP2J2 overexpression in endoithelial cells has anti-inflammatory effects.