Phospho-mTOR: A novel target in regulation of renal lipid metabolism abnormality of diabetes |
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Authors: | Jun Hao Lin Zhu Fan Li Qingjuan Liu Xue Zhao Shuxia Liu Lingling Xing Xiaojuan Feng Huijun Duan |
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Affiliation: | 1. Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China;2. Department of Electromyogram, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China |
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Abstract: | 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 wild-type 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. |
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Keywords: | mTOR SREBP-1 Lipogenesis Diabetic nephropathy Akt |
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