低出生体重大鼠肾组织中lncRNA表达谱的差异分析  

Differential Expression Profile of Long Non-coding RNA in the Kidneys of Low Birth Weight Rats

作　　者：黄慧 王雪芹[1] 孙云清 李根 李艳红[1,2] Huang Hui;Wang Xueqin;Sun Yunqing(Department of Nephrology,Children’s Hospital of Soochow University,Suzhou 215000,China)

机构地区：[1]苏州大学附属儿童医院肾脏科,苏州215000 [2]苏州大学附属儿童医院儿科临床研究院,苏州215000

出　　处：《华中科技大学学报（医学版）》2019年第6期644-649,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81741054);江苏省自然科学基金资助项目(No.BK20171217);苏州市临床重点病种诊疗技术专项基金资助项目(No.LCZX201611)

摘　　要：目的应用长链非编码RNA(lncRNA)基因芯片技术分析低出生体重(LBW)大鼠肾组织中lncRNA的表达情况。方法通过妊娠和哺乳期给予22%常规饲料建立Control组和6%低蛋白饲料建立LBW组大鼠模型。酸消化法计数生后10 d大鼠的肾小球数目;lncRNA芯片技术对两组大鼠肾脏表达的lncRNA进行差异筛选,生物信息学技术对差异显著的lncRNA与肾脏发育密切相关的编码基因mRNA行相关性分析。实时定量PCR(qRT-PCR)验证芯片结果并检测其在生后1 d和10 d大鼠肾组织中的表达水平。结果 LBW组大鼠生后1和10 d的体重、生后10 d的肾小球数目均低于Control组(均P<0.01),且肾小球数目与出生体重呈正相关(rs=0.73,P=0.003)。基因芯片和信息学分析显示两组差异表达的lncRNA 42个(折叠倍率≥2,P<0.05),其中16种lncRNA与丝裂原活化蛋白激酶4(MAPK4)mRNA表达显著相关(r=0.90,P<0.05)。qRT-PCR结果显示lncRNA TCONS00014139和TCONS00014138在生后1 d LBW组大鼠肾组织中相对高表达,生后10 d相对低表达,与肾单位数目呈正相关(P<0.01);lncRNA TCONS00017119在生后1和10 d LBW组肾组织持续高表达,与肾单位数目呈负相关(P=0.001)。结论两组大鼠肾组织中存在lncRNA的差异表达,且与肾脏发育密切相关的MAPK4 mRNA的表达有关,其中lncRNA TCONS00014139、TCONS00014138和TCONS00017119与肾单位数目显著相关,提示lncRNA在低出生体重大鼠肾脏发育障碍中可能发挥重要作用。Objective To investigate the long non-coding RNAs(lncRNAs)profiles in low birth weight(LBW)rat kidneys by using lncRNA array.Methods The rats at gestation and lactation were divided into control group and LBW group:Control group,fed with normal protein(22%)diets;LBW group,treated with low-protein(6%)diet.The total number of glomeruli per kidney in rats of 10 days old was determined using the maceration method.LncRNAs expression profiles were analyzed by using rat lncRNAs array and validated by using quantitative real-time PCR(qRT-PCR).Correlation analysis between differentially expressed lncRNAs and mRNAs involved in kidney development was performed.Results Birth weight was significantly lower in LBW rats than in controls 1 day and 10 days after birth(both P<0.01).The total number of glomeruli of rats of 10 days old was significantly lower in LBW rats than in control rats(P=0.001),and was positively related to birth weight(rs=0.73,P=0.003).Glomerular number was significantly positively correlated with the relative expression level of lncRNA TCONS00014139(P<0.01)and TCONS00014138(P<0.01),but negatively correlated with lncRNA TCONS00017119(P=0.001).Conclusion A number of lncRNAs were aberrantly expressed during nephron development in the kidneys of LBW rats compared with normal controls,and correlated with the expression of MAPK4 mRNA,which is involved in kidney development.The relative expression levels of lncRNA TCONS00014139,TCONS00014138,and TCONS00017119 were significantly correlated with glomerular number,indicating that these lncRNAs might play a potential role in renal dysplasia of LBW rats.

关 键 词：长链非编码RNA 低出生体重 肾发育 基因芯片 

分 类 号：R321.55[医药卫生—人体解剖和组织胚胎学]