An angiotensin II type 1 receptor blocker prevents renal injury via inhibition of the Notch pathway in Ins2 Akita diabetic mice.
An angiotensin II type 1 receptor blocker prevents renal injury via inhibition of the Notch pathway in Ins2 Akita diabetic mice.
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DOI：
10.1155/2012/159874
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发表时间：
2012
影响因子：
--
通讯作者：
Yokote K
中科院分区：
文献类型：
--
作者：
Koshizaka M;Takemoto M;Sato S;Tokuyama H;Fujimoto M;Okabe E;Ishibashi R;Ishikawa T;Tsurutani Y;Onishi S;Mezawa M;He P;Honjo S;Ueda S;Saito Y;Yokote K
近年来，有研究报道Notch通路参与糖尿病肾病的发病过程。在这项研究中，我们研究了Ins2秋田糖尿病小鼠（秋田小鼠）Notch通路的激活以及替米沙坦（一种血管紧张素II型受体阻滞剂）对Notch通路的影响。Notch1的胞内结构域（ICN1）在Notch激活过程中被蛋白水解从细胞质膜上切割。ICN1及其配体Jagged1在秋田小鼠肾小球中，尤其是足细胞中表达增加。替米沙坦可显著改善ICN1和Jagged1的表达。替米沙坦抑制血管紧张素ii诱导的可直接激活Notch信号通路的转化生长因子β和血管内皮生长因子A的表达升高。我们的研究结果表明，替米沙坦通过抑制Notch通路来预防糖尿病肾病。
Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse) and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1) is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor β and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway.
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