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中华肾病研究电子杂志 ›› 2020, Vol. 09 ›› Issue (05) : 207 -210. doi: 10.3877/cma.j.issn.2095-3216.2020.05.003

所属专题: 文献

论著

雷帕霉素通过调节mTOR-ULK1信号通路减轻高糖诱导的足细胞损伤
丁瑞1,(), 张月1, 余丹霞1, 牛伟辉1, 宋洁1, 吴玲玲2, 王述蔷2   
  1. 1. 101300 北京,北京市顺义区医院肾科
    2. 100853 北京,解放军总医院第一医学中心肾脏病科、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室
  • 收稿日期:2020-05-15 出版日期:2020-10-28
  • 通信作者: 丁瑞
  • 基金资助:
    国家自然科学基金项目(81870491); 北京市科委推广课题(Z191100006619001)

Rapamycin alleviated podocyte injury induced by high glucose via regulation of mTOR-ULK1 signaling pathway

Rui Ding1,(), Yue Zhang1, Danxia Yu1, Weihui Niu1, Jie Song1, Lingling Wu2, Shuqiang Wang2   

  1. 1. Department of Nephrology, Beijing Shunyi District Hospital, Beijing 101300
    2. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853, China
  • Received:2020-05-15 Published:2020-10-28
  • Corresponding author: Rui Ding
  • About author:
    Corresponding author: Ding Rui, Email:
引用本文:

丁瑞, 张月, 余丹霞, 牛伟辉, 宋洁, 吴玲玲, 王述蔷. 雷帕霉素通过调节mTOR-ULK1信号通路减轻高糖诱导的足细胞损伤[J/OL]. 中华肾病研究电子杂志, 2020, 09(05): 207-210.

Rui Ding, Yue Zhang, Danxia Yu, Weihui Niu, Jie Song, Lingling Wu, Shuqiang Wang. Rapamycin alleviated podocyte injury induced by high glucose via regulation of mTOR-ULK1 signaling pathway[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2020, 09(05): 207-210.

目的

探讨雷帕霉素对高糖环境下足细胞自噬和损伤作用的机制。

方法

体外培养永生化小鼠肾小球足细胞(mouse podocyte cell 5,MPC5)并进行分组:甘露醇等渗组(mannitol isotonic group,MG组)、高糖组( high glucose group,HG组)、雷帕霉素组(rapamycin group,RG组)以及自噬相关蛋白5-siRNA组(SiG组)。PCR和Western印迹检测足细胞标志Synaptopodin、自噬相关的ULK1以及mTOR通路相关蛋白p70S6K的表达。

结果

与MG组相比,HG组的Synaptopodin表达降低,自噬活性降低,p-ULK1以及p70S6K表达明显升高。与HG组相比,RG组的Synaptopodin表达升高,自噬活性较高,p-ULK1以及p70S6K表达较低。SiG组表现出与HG组相似的变化趋势。

结论

雷帕霉素可能通过mTOR-ULK1信号通路调节足细胞内自噬反应、减轻高糖环境引起的足细胞损伤。

Objective

To explore the specific mechanism of the effect of rapamycin on podocyte autophagy and damage under high glucose environment.

Methods

Cells of immortalized mouse podocyte cell 5 (MPC5) were cultured in vitro, and divided into several groups: mannitol isotonic group (MG), high glucose group (HG), rapamycin group (RG), and autophagy-related protein 5 (ATG5) siRNA group (SiG). PCR and Western blot were used to detect the expression of podocyte marker synaptopodin, autophagy-related ULK1 and mTOR pathway-related p70S6K.

Results

Compared with the MG group, the HG group showed lower levels of synaptopodin expression and autophagy activity, with significantly higher levels of p-ULK1 and p70S6K expression. Compared with the HG group, the RG group displayed higher levels of synaptopodin expression and autophagy activity, but showed lower levels of p-ULK1 and p70S6K expression. The SiG group showed a similar trend to the HG group.

Conclusion

Rapamycin alleviated the podocyte damage caused due to high glucose environment by regulating the autophagy reaction in podocytes through the mTOR-ULK1 signal pathway.

图1 足细胞标记蛋白、mTOR通路关键蛋白以及自噬相关蛋白表达情况比较
图2 Western印迹检测雷帕霉素的作用
图3 干预自噬相关蛋白后雷帕霉素的作用观察
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