精准医学杂志2024,Vol.39Issue(1):1-4,10,5.DOI:10.13362/j.jpmed.202401001
Sirt1对高糖诱导的足细胞外泌体释放的影响
Effect of Sirt1 on high glucose-induced exosome release from podocytes
摘要
Abstract
Objective To investigate the effect of nicotinamide adenine dinucleotide-dependent deacetylase 1(Sirt1)on high glucose-induced exosome release from podocytes.Methods Immortalized mouse podocytes MPC5 were divided into six groups:normal glucose group(5.5 mmol/L glucose,group A),high mannitol group(5.5 mmol/L glucose+24.5 mmol/L manni-tol,group B),high glucose group(30.0 mmol/L glucose,group C),high glucose+Sirt1-overexpressed lentivirus transfection group(Sirt1-overexpressed lentivirus transfection+30.0 mmol/L glucose,group D),high glucose+negative lentivirus transfection group(negative lentivirus transfection+30.0 mmol/L glucose,group E),and high glucose+exosome secretion inhibitor group(GW4869+30.0 mmol/L glucose,group F).Western blot was used to analyze the expression levels of Nephrin,Podocin,Sirt1,CD63,CD81,and Alix in each group.Real-time quantitative polymerase chain reaction was used to analyze the expression level of Sirt1 mRNA in D and E group.The morphology of podocyte exosomes was observed by a transmission electron microscope.The particle size and concentration of exosomes were determined by nanoparticle tracking analysis.Results The results of RT-qPCR showed that the relative expression of Sirt1 mRNA was significantly increased in group D compared with that in group E(t= 14.580,P<0.01).The results of nanoparticle tracking analysis and Western blot showed that the relative expression of Sirt1,Nephrin,and Podocin proteins in podocytes among groups A to C was significantly different(F=49.84-106.40,P<0.01).Com-pared with group A,group C had significantly increased secretion of podocyte exosomes(t=14.550,P<0.01)and significantly re-duced expression of Sirt1,Nephrin,and Podocin(t=7.446-15.110,P<0.01).Compared with group E,group D had significantly reduced release of podocyte exosomes(t=74.610,P<0.01)and significantly increased relative expression of Sirt1,Nephrin,and Podocin(t=4.657-32.860,P<0.05).Compared with group C,group F had significantly reduced release of podocyte exosomes(t=16.300,P<0.05)and significantly increased relative expression of Nephrin and Podocin(t=3.790,8.151,P<0.01),but showed no significant change in the expression level of Sirt1(P>0.05).Con-clusion Loss of Sirt1 in high glucose-treated podocytes promotes exosome secretion and podocyte injury.关键词
糖尿病肾病/血糖/足细胞/外泌体/抗衰老酶1Key words
Diabetic nephropathies/Blood glucose/Podocytes/Exosomes/Sirtuin 1分类
医药卫生引用本文复制引用
丁琳,周燕,刘珊珊,刘南池,马瑞霞..Sirt1对高糖诱导的足细胞外泌体释放的影响[J].精准医学杂志,2024,39(1):1-4,10,5.基金项目
山东省自然科学基金项目(ZR2022MH161) (ZR2022MH161)
青岛市医药卫生科研计划项目(2021-WJZD189) (2021-WJZD189)
青岛市民生科技计划项目(16-6-2-20-snh) (16-6-2-20-snh)
青岛大学附属医院临床医学+X项目(3390) (3390)
青岛市医疗卫生重点学科建设项目 ()