Phospho-mTOR: A novel target in regulation of renal lipid metabolism abnormality of diabetes
Phospho-mTOR: A novel target in regulation of renal lipid metabolism abnormality of diabetes
复制标题
DOI：
10.1016/j.yexcr.2013.06.013
复制
发表时间：
2013-08-15
影响因子：
3.7
通讯作者：
Duan, Huijun
中科院分区：
文献类型：
--
作者：
Hao, Jun;Zhu, Lin;Duan, Huijun
Akt的激活参与了糖尿病肾病的脂肪生成。然而，PI 3 K/Akt通路中的另一个主要基因mTOR是否也参与糖尿病肾脏脂肪生成尚不清楚。本研究发现，糖尿病大鼠肾小管上皮细胞中mTOR磷酸化水平上调，SREBP-1、ADRP和脂肪生成增加。再次，高糖增加磷酸化mTOR的表达，伴随着SREBP-1和ADRP的上调和脂质积聚在HKC细胞中。雷帕霉素（Rapamycin）是一种mTOR抑制剂，可抑制mTOR的激活，从而有效抑制高糖诱导的HKC细胞SREBP-1的上调和脂肪生成。此外，高糖刺激的HKC细胞转染野生型mTOR载体显示增强的SREBP-1和脂滴，然而，TE mTOR载体（激酶死亡）转染的HKC细胞呈现对高糖的抗性，并降低SREBP-1表达和脂肪生成。提示磷酸化mTOR介导了糖尿病肾小管细胞的脂质蓄积，可能成为治疗糖尿病肾病脂肪生成的潜在靶点。(C)2013 Elsevier Inc. All rights reserved.
The activation of Akt has been proved to involve in the lipogenesis of diabetic nephropathy. However, it's still not clear whether mTOR, another main gene in PI3K/Akt pathway, is also involved in the renal lipogenesis of diabetes. In the present study, it was revealed that the phosphorylation of mTOR was up-regulated in the renal tubular cells of diabetic rats, followed by the over-expression of SREBP-1, ADRP and lipogenesis. Again, high glucose increased the expression of phospho-mTOR accompanied with SREBP-1 and ADRP up-regulation and lipid accumulation in HKC cells. Rapamycin, known as mTOR inhibitor, was used to inhibit the activation of mTOR, which prevented effectively high glucose-induced SREBP-1 up-regulation and lipogenesis in HKC cells. Furthermore, high glucose-stimulated HKC cells transfected with wildtype mTOR vector showed the enhanced SREBP-1 and lipid droplets, however, TE mTOR vector (kinase dead)-transfected HKC cells presented resistance to high glucose and decreased SREBP-1 expression and lipogenesis. These above data suggested that phospho-mTOR mediated lipid accumulation in renal tubular cells of diabetes and might be the potential targets for treating lipogenesis of diabetic nephropathy. (C) 2013 Elsevier Inc. All rights reserved.