切换至 "中华医学电子期刊资源库"

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]. 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]. 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
[1]
Heerspink HJL, Andress DL, Bakris G, et al. Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial: a clinical trial design novel to diabetic nephropathy [J]. Diabetes Obes Metab, 2018, 20(6): 1369-1376.
[2]
Kobayashi K, Shibata M, Kato K. Diabetic nephropathy [J]. Naika, 1971, 27(6): 1431-1437.
[3]
Hoffmann S, Podlich D, Hahnel B, et al. Angiotensin II type 1 receptor overexpression in podocytes induces glomerulosclerosis in transgenic rats [J]. J Am Soc Nephrol, 2004, 15(6): 1475-1487.
[4]
Singh L, Singh G, Dinda AK. Understanding podocytopathy and its relevance to clinical nephrology [J]. Indian J Nephrol, 2015, 25(1): 1-7.
[5]
Hartleben B, Godel M, Meyer-Schwesinger C, et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice [J]. J Clin Invest, 2010, 120(4): 1084-1096.
[6]
Mori H, Inoki K, Masutani K, et al. The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential [J]. Biochem Biophys Res Commun, 2009, 384(4): 471-475.
[7]
Yang Y, Wang J, Qin L, et al. Rapamycin prevents early steps of the development of diabetic nephropathy in rats [J]. Am J Nephrol, 2007, 27(5): 495-502.
[8]
Asanuma K, Tanida I, Shirato I, et al. MAP-LC3, a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis [J]. FASEB J, 2003, 17(9): 1165-1167.
[9]
Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues [J]. Cell, 2011, 147(4): 728-741.
[10]
Levine B, Yuan J. Autophagy in cell death: an innocent convict? [J]. J Clin Invest, 2005, 115(10): 2679-2688.
[11]
Klionsky DJ, Abeliovich H, Agostinis P, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes [J]. Autophagy, 2008, 4(2): 151-175.
[12]
Weide T, Huber TB. Implications of autophagy for glomerular aging and disease [J]. Cell Tissue Res, 2011, 343(3): 467-473.
[13]
Shankland SJ. The podocyte′s response to injury: role in proteinuria and glomerulosclerosis [J]. Kidney Int, 2006, 69(12): 2131-2147.
[14]
Velagapudi C, Bhandari BS, Abboud-Werner S, et al. The tuberin/mTOR pathway promotes apoptosis of tubular epithelial cells in diabetes [J]. J Am Soc Nephrol, 2011, 22(2): 262-273.
[1] 李康, 冀亮, 赵维, 林乐岷. 自噬在乳腺癌生物学进展中的双重作用[J]. 中华乳腺病杂志(电子版), 2023, 17(04): 195-202.
[2] 孔莹莹, 谢璐涛, 卢晓驰, 徐杰丰, 周光居, 张茂. 丁酸钠对猪心脏骤停复苏后心脑损伤的保护作用及机制研究[J]. 中华危重症医学杂志(电子版), 2023, 16(05): 355-362.
[3] 陈玲, 李楠, 杨建乐. 微小RNA-377-3p调控自噬改善脂多糖/D-半乳糖胺诱导的急性肝衰竭的机制研究[J]. 中华危重症医学杂志(电子版), 2023, 16(02): 89-97.
[4] 周子慧, 李恭驰, 李炳辉, 王知, 刘慧真, 王卉, 邹利军. 细胞自噬在创面愈合中作用的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 542-546.
[5] 张永博, 张亮, 陈浏阳, 戴睿, 孙华, 杨盛, 孟博, 彭晴. 线粒体与椎间盘退变[J]. 中华损伤与修复杂志(电子版), 2023, 18(03): 265-269.
[6] 钟文涛, 赵阳, 沈晓菲, 杜峻峰. 自噬在脓毒症中的作用及靶向治疗研究进展[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 221-225.
[7] 中国器官移植发展基金会器官移植受者健康管理专家委员会, 中国医师协会器官移植医师分会, 中华医学会器官移植学分会, 国家肝脏移植质控中心. 肝移植受者雷帕霉素靶蛋白抑制剂临床应用中国专家共识(2023版)[J]. 中华移植杂志(电子版), 2023, 17(04): 193-204.
[8] 邵浩仁, 郭佳. 铁死亡的分子机制及其在前列腺癌治疗中的研究进展[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 294-298.
[9] 莫钊鸿, 翟航, 苏日顺, 孟泓宇, 罗豪, 陈文豪, 许瑞云. U2AF2表达对肝细胞癌增殖和迁移的影响及其与预后的关系[J]. 中华肝脏外科手术学电子杂志, 2023, 12(03): 336-341.
[10] 王小红, 钱晶, 翁文俊, 周国雄, 朱顺星, 祁小鸣, 刘春, 王萍, 沈伟, 程睿智, 秦璟灏. 巯基丙酮酸硫基转移酶调控核因子κB信号介导自噬对重症急性胰腺炎大鼠的影响及机制[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 422-426.
[11] 刘新献, 王雅琪, 周斌, 郭严延. 雷帕霉素在兔腐蚀性食管炎性狭窄早期干预中的意义[J]. 中华介入放射学电子杂志, 2023, 11(04): 324-329.
[12] 郭如烨, 孟黎明, 陈楠, 宋玉莹, 尹海燕, 郭岩. Apelin/APJ系统对帕金森病模型的神经保护作用及机制研究进展[J]. 中华诊断学电子杂志, 2023, 11(04): 276-282.
[13] 李民昌, 马长林. 自噬调控的细胞铁死亡及在肿瘤中影响的研究进展[J]. 中华诊断学电子杂志, 2023, 11(02): 140-144.
[14] 李正达, 张艳兵, 刘茂霞, 李玉芳, 杨新静. 艾司洛尔对脓毒症肠损伤的保护作用及对自噬蛋白AMPK表达水平的影响[J]. 中华卫生应急电子杂志, 2023, 09(02): 90-95.
[15] 邱甜, 杨苗娟, 胡波, 郭毅, 何奕涛. 亚低温治疗脑梗死机制的研究进展[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 518-521.
阅读次数
全文


摘要