Development of CYP2J2 gene therapy for glomeruonephritis and diabetic nephropathy

CYP2J2是花生四烯酸生成环氧二碳三烯酸的关键调控因子。环氧二碳三烯酸是一种血管扩张剂，可以放松血管平滑肌细胞，并对血管细胞具有抗炎特性。因此，提示在系膜细胞和内皮细胞中诱导CYP2J2基因通过改善血流和抗炎作用对肾脏具有保护作用。我们研究了促进血管细胞氧化应激和炎症的血管紧张素II对CYP2J2基因表达的影响。我们通过RT-PCR证实了在培养的内皮细胞和系膜细胞中CYP2J2 mRNA的表达增加。肿瘤坏死因子-a是一种炎性细胞因子，对培养的内皮细胞和系膜细胞中CYP2J2 mRNA的表达有相似的影响。这些数据表明炎症刺激增加了内皮细胞和系膜细胞中CYP2J2 mRNA的表达。此外，我们还证明，在培养的内皮细胞中，肿瘤坏死因子-α-诱导的细胞间粘附分子-1的表达通过过表达CYP2J2而降低。提示内皮细胞中CYP2J2过表达具有抗炎作用。

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.