Potential role of microRNA-503 in Icariin-mediated prevention of high glucose-induced endoplasmic reticulum stress  

作　　者：Bao-Lin Su Liang-Liang Wang Liang-You Zhang Shu Zhang Qiang Li Gang-Yi Chen 

机构地区：[1]Department of Nephrology,The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,Guangdong Province,China

出　　处：《World Journal of Diabetes》2023年第8期1234-1248,共15页世界糖尿病杂志（英文版）（电子版）

基　　金：The First Affiliated Hospital of Guangzhou University of Chinese Medicine Innovation and Strengthening Fund,No.2019QN14.

摘　　要：BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediated apoptosis in high glucose(HG)-induced primary rat kidney cells(PRKs),with emphasis on the role of miR-503 and sirtuin 4(SIRT4)in this process.METHODS Single intraperitoneal injection of streptozotocin(65 mg/kg)in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model.Glucose-treated PRKs were used as an in vitro HG model.An immunofluorescence assay identified isolated PRKs.Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis,respectively.Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stressrelated proteins.Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.RESULTS ICA treatment alleviated the upregulated miR-503 expression in vivo(DN)and in vitro(HG).Mechanistically,ICA reduced HG-induced miR-503 overexpression,thereby counteracting its function in downregulating SIRT4 levels.ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.CONCLUSION ICA reduced HG-mediated inhibition of cell viability,promotion of apoptosis,and ER stress in PRKs.These effects involved regulation of the miR-503/SIRT4 axis.These findings indicate the potential of ICA to treat DN,and implicate miR-503 as a viable target for therapeutic interventions in DN.

关 键 词：ICARIIN MicroRNA-503 Sirtuin 4 Endoplasmic reticulum stress Diabetic nephropathy Kidney damage 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]