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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Cyanidin-3-O-glucoside attenuates high glucose-induced podocyte dysfunction by inhibiting apoptosis and promoting autophagy via activation of SIRT1/AMPK pathway
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Cyanidin-3-O-glucoside attenuates high glucose-induced podocyte dysfunction by inhibiting apoptosis and promoting autophagy via activation of SIRT1/AMPK pathway

机译:Cyanidin-3-O-葡糖苷通过抑制细胞凋亡并通过SIRT1 / AMPK途径的激活抑制凋亡和促进自噬能量

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摘要

Diabetic nephropathy (DN) is a common and complicated chronic kidney disease around the world. To elucidate and find effective therapies of DN is of vital importance. In this paper, we have discovered that cyanidin-3-O-glucoside (C3G), which is one of the anthocyanins, could alleviate high glucose-induced podocyte dysfunction. MTT, flow cytometry assay, and Western blot analysis showed that C3G could reverse the increase of cell apoptosis under high glucose treatment in MPC5 cells by upregulation of Bcl2 and downregulation of Bax and cleaved caspase-3. Moreover, C3G improved the autophagy decrease that was induced by high glucose through regulating the expression level of LC3-II/LC3-I, Beclin1, and p62. In addition, C3G inhibited epithelial-mesenchymal transition (EMT) by increasing E-cadherin and reducing Vimentin. By further study of the mechanisms, we found C3G activated the SIRT1 and AMPK which were inhibited in high glucose condition. Silencing SIRT1 blocked the effect of C3G on regulating cell apoptosis, autophagy, and EMT. In summary, our current findings suggest the protective effect of C3G against high glucose-induced podocyte dysfunction is by improving autophagy and reducing apoptosis and EMT via activating SIRT1/AMPK pathway. It might be a new insight for the treatment of DN.
机译:糖尿病肾病(DN)是一种常见且复杂的慢性肾脏疾病。阐明并找到有效的DN治疗方法至关重要。在本文中,我们发现花青素中的花青素-3-O-葡萄糖苷(C3G)可以缓解高糖诱导的足细胞功能障碍。MTT、流式细胞术和Western blot分析表明,C3G可通过上调Bcl2、下调Bax和切割的caspase-3,逆转高糖处理下MPC5细胞凋亡的增加。此外,C3G通过调节LC3-II/LC3-I、Beclin1和p62的表达水平,改善了高糖诱导的自噬减少。此外,C3G通过增加E-钙粘蛋白和降低波形蛋白来抑制上皮-间质转化(EMT)。通过进一步的机制研究,我们发现C3G激活了在高糖条件下被抑制的SIRT1和AMPK。沉默SIRT1可阻断C3G对细胞凋亡、自噬和EMT的调节作用。总之,我们目前的研究结果表明,C3G对高糖诱导的足细胞功能障碍的保护作用是通过激活SIRT1/AMPK途径改善自噬,减少细胞凋亡和EMT。这可能是DN治疗的一个新视角。

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