期刊
MOLECULAR MEDICINE REPORTS
卷 18, 期 2, 页码 1789-1797出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2018.9085
关键词
glucagon-like peptide-1; sirtuin 1; high glucose; caspase-3; caspase-9
资金
- Changhai Hospital [CH 201508]
Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that is considered to be a promising target for the treatment of patients with type 2 diabetes. However, the mechanisms underlying the protective effects of GLP-1 on diabetic nephropathy are yet to be fully elucidated. Sirtuin (SIRT)1 encodes a member of the SIRT family of proteins that serves an important role in mitochondrial function and is reported to be associated with the pathogenesis of chronic kidney disease. The present study treated mouse podocytes with various concentrations of D-glucose to establish a high glucose (HG)-induced model of renal injury. The results of a 2,7-dichlorodihydrofluorescein diacetate assay, Annexin V/propidium iodide staining and ELISA demonstrated that treatment of podocytes with HG significantly enhanced the production of reactive oxygen species (ROS), promoted cell apoptosis and increased the secretion of proinflammatory cytokines, respectively. The cytokines increased following HG treatment included tumor necrosis factor-, interleukin (IL)-1 and IL-6. Notably, treatment with GLP-1 attenuated HG-induced increases in ROS production and podocyte apoptosis, which may occur via downregulation of the expression of caspase-3 and caspase-9, and increased expression of nephrin, podocin and SIRT1, as determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Treatment with GLP-1 led to protective effects in podocytes that were similar to those of resveratrol. Furthermore, SIRT1 knockdown using short hairpin RNA significantly enhanced the expression of caspase-3 and caspase-9 in mouse podocytes, compared with normal mouse podocytes. SIRT1 knockdown with or without GLP-1 administration significantly decreased the expression of caspase-3 and caspase-9 in mouse podocytes, compared with SIRT1 knockdown mouse podocytes. In conclusion, the results of the present study indicated that GLP-1 may be a promising target for the development of novel therapeutic strategies for HG-induced nephropathy, and may function through the activation of SIRT1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据