肾脏VDR表达与衰老密切相关-来自多个数据库的综合分析  

Renal VDR expression is closely associated with aging:A comprehensive analysis from multiple databases

作　　者：吴好 周小兰 倪挺 游怀舟 陈靖 Wu Hao;Zhou Xiaolan;Ni Ting;You Huaizhou;Chen Jing(Department of Nephrology,Huashan Hospital,Fudan University,Shanghai,200040,P.R.China;Institute of Human Phenotype Group Research,Fudan University,Shanghai,200438,P.R.China;National Clinical Medical Research Center for Geriatric Diseasest Huashan Hospital,Fudan University,Shanghai,200040,P.R.China)

机构地区：[1]复旦大学附属华山医院肾病科,上海200040 [2]复旦大学人类表型组研究院,上海200438 [3]国家老年疾病临床医学研究中心(华山),上海200040

出　　处：《老年医学与保健》2023年第4期779-784,788,共7页Geriatrics & Health Care

基　　金：国家重点研发计划(2021YFC2500202,2020YFC2005000);上海市科学技术委员会“科技创新行动计划”(20Y11904500,21ZR1411100)。

摘　　要：目的维生素D缺乏是老年人常见的健康问题。肾脏是产生活性维生素D的重要器官,也是维生素D受体(Vitamin D receptor,VDR)表达较多的器官之一。作为体内最早发生衰老的器官之一,肾脏VDR缺乏与肾脏衰老的关系既往未见报道。本研究拟通过人类和小鼠数据库分析,探究肾脏VDR表达随增龄的变化及与肾脏衰老的关系,并在动物中进行验证。方法首先通过人类和小鼠公共数据库明确肾脏VDR的表达情况;其次对VDR高表达器官分析VDR随增龄的变化趋势,通过免疫组化及免疫印迹方法在6月、15月、21月龄的雄性野生型小鼠肾组织中进行验证;对上述野生型小鼠肾组织进行p16免疫组化染色,并进行VDR和p16的相关性分析;最后,基于基因表达微阵列进行基因富集分析(Gene Set Enrichment Analysis,GSEA),在人类肾脏数据中探索与肾小球VDR相关的生物学途径。结果人类和小鼠数据库都提示肾脏是VDR表达最多的器官之一,随着增龄,肾脏VDR的表达呈下降趋势。基于基因表达微阵列的GSEA分析显示低VDR表达组富集更多的衰老基因。野生型小鼠肾脏免疫组化和免疫印迹结果提示肾脏VDR表达随增龄下降,且与衰老标记物p16的表达呈负相关。结论肾脏VDR表达随增龄下降,参与衰老相关生物学途径,VDR表达降低与衰老标记物增加密切相关。Objective Vitamin D deficiency is a common health problem in the elderly.The kidney is an important organ that produces active vitamin D and is also one of the organs with high expression of vitamin D receptor(VDR).As one of the earliest aging organs in the body,the relationship between renal VDR deficiency and renal aging has not been reported in the past.This study aims to investigate the changes of renal VDR expression with aging and its relationship with renal aging by analyzing human and mouse databases,and verify them in animals.Methods Firstly,the expression of renal VDR was determined through public databases of humans and mice.Secondly,the trend of VDR changes with aging was analyzed for organs with high expression of VDR.Immunohistochemical and Western blotting methods were used to validate the changes in renal tissue of male wild-type mice aged 6,15,and 21 months.The renal tissues of the above wild type mice were stained with pl6 immunohistochemistry,and the correlation between VDR and pl6 was analyzed.Finally,Gene set enrichment analysis(GSEA)based on gene expression microarray was used to explore biological pathways related to glomerular VDR in human kidney database.Results Both human and mouse databases suggested that kidney was one of the organs with the highest expression of VDR,and the expression of VDR in kidney tendedto decline with aging.GSEA analysis based on gene expression microarrays showed that the low VDR expression group was enriched with more aging genes.Renal immunohistochemistry and Western blot results of wild-type mice indicated that the expression of VDR in the kidneys decreased with aging and was negatively correlated with the expression of aging marker pl6.Conclusion The expression of VDR in the kidneys decreases with agingand it is involved in aging-related biological pathways.The decrease of VDR expression is closely related to the increase of aging markers.

关 键 词：肾脏 维生素D受体 衰老 

分 类 号：R692[医药卫生—泌尿科学]