Co-regulation of SREBP-1 and mTOR ameliorates lipid accumulation in kidney of diabetic mice
Co-regulation of SREBP-1 and mTOR ameliorates lipid accumulation in kidney of diabetic mice
复制标题
SREBP-1 和 mTOR 的共同调节改善糖尿病小鼠肾脏中的脂质积累
DOI：
10.1016/j.yexcr.2015.06.006
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发表时间：
2015
影响因子：
3.7
通讯作者：
Liu Wei
中科院分区：
文献类型：
--
作者：
Wang Hui;Zhu Lin;Hao Jun;Duan Huijun;Liu Shuxia;Zhao Song;Liu Qingjuan;Liu Wei
SREBP-1和mTOR参与糖尿病肾脏脂质代谢。在本研究中，我们使用糖尿病小鼠和培养的肾小管细胞研究SREBP-1和mTOR的共调节对肾脏脂质代谢的影响。结果显示，与单独转染shRNA-SREBP-1载体的HKC细胞相比，shRNA-SREBP-1载体和激酶死亡mTOR载体共转染的HKC细胞中SREBP-1蛋白表达水平显著降低64.1%，同时FcB mRNA、ACC mRNA、ADRP蛋白和脂滴水平也明显降低。与单独注射shRNA-SREBP-1载体的糖尿病小鼠相比，联合注射shRNA-SREBP-1载体和激酶死亡mTOR载体的糖尿病小鼠肾脏SREBP-1蛋白、FRES 1 mRNA和ACC mRNA分别降低34.6%、45.9%和22.0%，同时伴有ADRP蛋白和甘油三酯含量的降低。最后，我们的研究表明，SREBP-1和mTOR在糖尿病小鼠肾脏中的共同调节比仅调节SREBP-1更有效地降低肾脏脂肪生成。
SREBP-1 and mTOR have been proved to involve in renal lipid metabolism of diabetes mellitus. In the present study, we investigated the effect of co-regulation of SREBP-1 and mTOR on renal lipid metabolism using diabetic mice and cultured renal tubular cells. The results showed that compared with those in high glucose-stimulated HKC cells single transfected with shRNA-SREBP-1 vector, the level of SREBP-1 protein were significantly reduced by 64.1% followed by decreased FASN mRNA, ACC mRNA, ADRP protein and lipid droplets in HKC cells co-transfected with shRNA-SREBP-1 vector and kinase-dead mTOR vector. Furthermore, diabetic mice co-injected with shRNA-SREBP-1 vector and kinase-dead mTOR vector showed that renal SREBP-1 protein, FASN mRNA and ACC mRNA were respectively decreased by 34.6%, 45.9%, 22.0% in comparison with those in diabetic mice single injected with shRNA-SREBP-1 vector accompanied by reduced ADRP protein and triglyceride content. In the end our study suggests that co-regulation of SREBP-1 and mTOR in kidney of diabetic mice is more effective in lowering renal lipogenesis than only regulation of SREBP-1.