Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway.
Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway.
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DOI：
10.3892/ijmm.2017.2864
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发表时间：
2017-03
影响因子：
5.4
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Huang G;Zou B;Lv J;Li T;Huai G;Xiang S;Lu S;Luo H;Zhang Y;Jin Y;Wang Y
终末分化足细胞损伤是蛋白尿和肾小球硬化的重要原因。本研究旨在探讨三七皂苷R1 （NR1）通过抑制凋亡、诱导自噬和维持靶细胞足细胞生物学，维持足细胞数量和足突结构的保护作用。通过观察NR1对高糖条件下人足细胞凋亡率、自噬率和狭缝膜蛋白表达水平的影响，探讨NR1对高糖条件下人足细胞条件永生化的影响。我们的研究结果表明NR1通过减少细胞凋亡、增加自噬和促进细胞骨架恢复来保护足细胞免受高糖诱导的损伤。为了阐明NR1对足细胞保护作用的机制，我们进一步研究了PI3K /Akt/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。我们的数据表明，NR处理增加了PI3K、Akt和mTOR的磷酸化水平，导致足细胞中PI3K/Akt/mTOR信号通路的激活。据我们所知，这是首次在体外研究中证明NR1通过激活PI3K/Akt/mTOR通路来保护足细胞。
Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins. Our results revealed that NR1 protected the podocytes against high glucose-induced injury by decreasing apoptosis, increasing autophagy and by promoting cytoskeletal recovery. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was further investigated in order to elucidate the mechanisms responsible for the protective effects of NR1 on podocytes. Our data indicated that treatment with NR increased the phosphorylation levels of PI3K, Akt and mTOR, leading to the activation of the PI3K/Akt/mTOR signaling pathway in podocytes. To the best of our knowledge, this is the first in vitro study to demonstrate that NR1 protects podocytes by activating the PI3K/Akt/mTOR pathway.