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Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway

查看全文 作　　者：Dong-wei [1,2]CAO;Chun-ming [1,2]JIANG;Cheng [2]WAN;Miao [2]ZHANC;Qing-yan [2]ZHANG;Min [2]ZHAO;Bo [3]YANG;Da-long [4]ZHU;Xiao [5]HAN 高影响力作者 机构地区：[1]Department of Nephrology,Nanjing Drum Tower Hospital,Clinical College of Nanjing Medical University,Nanjing 210008,China;[2]Department of Nephrology,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China;[3]Department of Dermatology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;[4]Department of Endocrinology,Nanjing Drum Tower Hospital,Clinical College of Nanjing Medical University,Nanjing 210008,China;[5]Basic Medical School,Naniing Medical University,Nanjing 210000,China高影响力机构 出　　处：《Current Medical Science》索引2018年第38卷第5期,共7页高影响力期刊 基　　金：This project was supported by grants from the Key Science and Technology Development Program of Nanjing City of the People's Republic of China (No. YKK15057 and No.YKK16097)and the National Natural Science Foundation of China (No.81473684). 摘　　要：Diabetic kidney disease (DKD)is a microvascular complication of type 2 diabetes.The study of DKD mechanisms is the most important target for the prevention of DKD.Renal senescence is one of the important pathogeneses for DKD,but the mechanism of renal and cellular senescence is unclear.Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD.This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs)induced by high glucose.HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640)in vitro.The effect of high glucose on morphology of HGMCs was observed 72h after intervention.The cell cycle was examined by flow cytometry.The telomere length was measured by Southern blotting.The expression levels of p53,p21 and Rb proteins in p53-p21-Rb signaling pathway and p-statl,p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively.The expression of miR-126 was examined by qRT-PCR.MiR-126 mimics was transfected into HGMCs.The effects of miR-126 mimics transfection on cell morphology,cell cycle,telomere length,p53,p21,Rb,p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1phase but also shortened the telomere length.High glucose led to high expression of p53,p21,Rb,p-statl and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways.Moreover,the miR-126 was decreased in HGMCs induced by high glucose.It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs.The results may serve as a new strategy for the treatment of DKD. 关 键 词：diabetic kidney disease MIR-126 human glomerular mesangial cells SENESCENCE telomere-p53-p21-Rb signaling pathway
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