不同年龄段人群尿液外泌体中miR-150-5p对肾脏衰老的影响  

Effects of urinary exosomal miR-150-5p on renal senescence in different age groups

作　　者：王珊[1] 马清[1] 杨华昱[1] 姚兰[1] 丁宁 Wang Shan;Ma Qing;Yang Huayu;Yao Lan;Ding Ning(Department of Geriatrics,Beijing Friendship Hospital,Capital Medical University,Beijing,100050,China;Department of Emergency,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院老年医学科,100050 [2]首都医科大学附属北京友谊医院急诊科,100050

出　　处：《中华老年医学杂志》2021年第11期1386-1391,共6页Chinese Journal of Geriatrics

基　　金：国家自然科学基金资助项目(No.81601210);北京市医院管理局"青苗"计划(QML20170103)

摘　　要：目的探讨尿液外泌体miR-150-5p在不同年龄段人群中表达量的变化及miR-150-5p在肾脏衰老过程中的作用.方法选择2014年1月至2016年12月于北京友谊医院老年医学科就诊的76例为研究对象,其中青年组15例,中年组35例,老年组26例,提取尿液外泌体,利用实时定量荧光PCR法检测miR-150-5p表达情况,并通过Logistic回归分析评估不同含量miR-150-5p与年龄、性别、高血压病史、冠心病病史、高脂血症之间的相关性;在人肾小管上皮细胞HK2细胞中过表达和敲低miR-150-5p后,通过蛋白质印迹法分析HK-2细胞中上皮细胞黏附分子相关蛋白表达量情况;通过细胞学实验明确miR-150-5p过表达或敲低后对HK-2细胞增殖、细胞周期的影响.结果Logistic回归分析发现年龄与尿液外泌体中miR-150-5p相对含量密切相关(P<0.05),老年组尿液外泌体内miR-150-5p相对含量(1.33±0.41)较青年组(0.88±0.40)明显增加(P<0.05),且随着年龄增长,尿液外泌体内miR-150-5p相对含量与肾小球滤过率水平成反比.体外实验发现在肾小管上皮细胞HK-2中敲低miR-150-5p后上皮细胞黏附分子Zo-1、E-Cadherin表达量略有下降;而过表达miR-150-5p后,Zo-1、E-Cadherin表达略有增高,miR-150-5p可能影响HK-2细胞的凋亡.结论尿液外泌体miR-150-5p在老年组人群中表达量略有增加,且与肾功能相关;miR-150-5p可影响肾小管上皮细胞中部分上皮细胞黏附分子相关蛋白的表达,有望成为肾脏衰老相关性基因之一.Objective To investigate the expression of urinary exosomal miR-150-5p in different age groups and its relationship with kidney aging.Methods Seventy-six subjects were recruited at the geriatrics department of Beijing Friendship Hospital from January 2014 to December 2016»with 15 in the young group,35 in the middle-aged group,and 26 in the elderly group.We detected the expression of urinary exosomal miR-15O-5p by real-time PCR from urine samples of different age groups and used Logistic regression analysis to evaluate the correlation of different levels of miR-150-5p with age,gender*history of hypertension,history of coronary heart disease,and hyperlipidemia.Additionally after overexpression and knockdown of miR-150-5p in human renal tubular cells of the HK2 cell line,we analyzed the expression levels of epithelial-to-mesenchymal transition(EMT)-related proteins by Western blotting.Results Logistic regression analysis showed that age was closely related to estimated urinary exosomal miR-150-5p levels(P<0.05),and estimated urinary exosomal miR-150-5p levels in the elderly group(1.33±0.41)were significantly higher than those in the young group(0.88±0.40)(P<0.05).In addition,estimated urinary exosomal miR-150-5p levels became inversely proportional to the glomerular filtration rate as age increased.In vitro experiments showed that the expression levels of ZO-1 and E-cadherin in epithelial cells were slightly decreased after knockdown of miR-150-5p in renal tubular epithelial cells of the HK-2 cell line.Conclusions The expression of miR-15O-5p in urinary exosomes may be slightly increased in the elderly.It could inhibit the occurrence of renal EMT,and its expression is correlated with renal function.Mir-150-5p may also affect the expression of adhesion molecule-related proteins in HK-2 cells.MiR-150-5p in urinary exosomes is expected to become one of the genetic markers associated with renal aging.

关 键 词：肾脏 衰老 尿 外泌体 微小RNA miR-150-5p 

分 类 号：R446.12[医药卫生—诊断学]