Development of CYP2J2 gene therapy for glomeruonephritis and diabetic nephropathy

CYP2J2基因治疗肾小球肾炎和糖尿病肾病的进展

• 批准号: 17590832
• 负责人: MIYAZONO Motoaki
• 金额: $ 1.92万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590832/
• 关键词: kidney disease; diabetes mellitus; CYP2J2

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.

CYP2J2 是花生四烯酸生产环氧二十碳三烯酸的重要调节因子。环氧二十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，表明系膜细胞和内皮细胞中CYP2J2基因的诱导通过改善血流和抗炎作用显示出对肾脏的保护作用。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 证明了培养的内皮细胞和系膜细胞中 CYP2J2 mRNA 表达增加。肿瘤坏死因子-a 是一种炎症细胞因子，对培养的内皮细胞和系膜细胞中的 CYP2J2 mRNA 表达显示出类似的影响。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，培养的内皮细胞中CYP2J2的过表达会降低肿瘤坏死因子-α诱导的细胞间粘附分子-1的表达。该结果表明CYP2J2在内皮细胞中过表达具有抗炎作用。

项目成果

糖尿病患者における心血管合併症の予防と治療 食後高血糖による血管内皮機能の障害とその制御

糖尿病患者心血管并发症的防治、餐后高血糖引起的血管内皮功能损伤及其控制

• 发表时间: 2005
• 期刊: 糖尿病合併症 19巻1号
• 作者: Nagase M;et al.;野出孝一
• 通讯作者: 野出孝一

Partial blood recirculation : A new trial for prolonging filter life during continuous hemodiafiltration.

部分血液再循环：一项延长连续血液透析滤过期间过滤器寿命的新试验。

• 发表时间: 2007
• 期刊: Ther Aphe (In press)
• 作者: Ikeda Y;Kishi T;Kishi C;Miyazono M;Ohtsubo S;Nakashima M;Sakemi T;Ando T;Node K
• 通讯作者: Node K

血管障害への影響

对血管疾病的影响

• 发表时间: 2005
• 期刊: 糖尿病学の進歩 39集
• 作者: Shibata S;et al.;野出孝一
• 通讯作者: 野出孝一

外因性NO供与の臨床的意義・血管弛緩因子のNOとEETの関係

外源性NO供应的临床意义/血管舒张剂NO与EET的关系

• 发表时间: 2005
• 期刊: Therapeutic Research 26巻2号
• 作者: Usui HK;Shikata K;Sasaki M;Okada S;Matsuda M;Shikata Y;Ogawa D;Kido Y;Nagase R;Yozai K;Ohga S;Tone A;Wada J;Takeya M;Horiuchi S;Kodama T;Makino H.;野出孝一
• 通讯作者: 野出孝一