VEGF-A对小鼠肾脏促红细胞生成素调控作用研究  

VEGF-A Regulates Erythropoietin Expression in the Kidney of a Mouse Model

作　　者：吕飞 丁亦男 张智慧 张继旭 刘思奇 张景斌 芦小单[1,2] LU Fei;DING Yi-nan;ZHANG Zhi-hui;ZHANG Ji-xu;LIU Si-qi;ZHANG Jing-bin;LU Xiao-dan(College of Sciences,Changchun Normal University,Changchun 130032,China;Jilin Provincial People’s Hospital,Changchun 130021,China)

机构地区：[1]长春师范大学生命科学学院,吉林长春130032 [2]吉林省人民医院,吉林长春130021

出　　处：《长春师范大学学报》2023年第4期120-125,共6页Journal of Changchun Normal University

基　　金：2022年吉林省科技厅创新人才(团队)项目“吉林省精准医疗多组学研究创新团队”(20220508080RC);吉林省科技厅自然科学基金项目“VEGFA参与调控慢性淋巴细胞性甲状腺炎发生发展的机制研究”(YDZJ2022012YTS148);吉林省卫健委“肺腺癌LKB1基因突变分子检测体系及临床研究”(2022JC002);国家自然科学基金中日合作项目“血管内皮生长因子参与调控脂肪组织纤维化和能量平衡的机制研究”(32011540004);国家自然科学基金青年项目“脂肪组织中维持线粒体稳定性的时空网络调控机制研究”(31900823)。

摘　　要：为了研究血管内皮生长因子VEGF-A对肾脏促红细胞生成素EPO的表达调控以及相关基因和通路的影响,我们利用VEGF可逆抑制小鼠模型,将小鼠模型分为VEGF-A正常组(dox+)和VEGF-A抑制组(dox-)(n=8)。取小鼠肾脏组织提取总RNA,qPCR检测VEGF-A以及部分相关基因的mRNA表达量,进行转录组测序,通过FPKM和log_(2)(FC)一值筛选差异基因进行GO和KEGG通路富集分析。结果发现,dox-组较dox+组VEGF-AmRNA水平明显降低;两组小鼠转录组测序数据分析发现共有1 282个差异基因,其中上调基因803个,下调基因479个;通过对差异基因进行GO和KEGG富集分析发现,差异基因主要参与T细胞活化、脂肪细胞分化产热等,主要定位在细胞外基质以及质膜外侧等位置,且富集于PI3K-AKT信号通路。因此我们得出结论,抑制小鼠VEGF-A的表达可以促进EPO表达上调,从而影响PI3K-AKT信号通路相关基因水平表达。In order to investigate the effect of Vascular Endothelial Growth Factor(VEGF-A)on the expression and regulation of renal Erythropoietin(EPO)and related genes and pathways,we used mouse model of reversible inhibition of VEGF,which was divided into normal VEGF-A group(dox+)and VEGF-A inhibitory group(dox-)(n=8).Total RNA was extracted from mouse kidney tissue,and mRNA expression levels of VEGF-A and some related genes were detected by qPCR.Transcriptome sequencing was performed,and differential genes were screened by FPKM and log_(2)(FC)values for enrichment analysis of GO and KEGG pathways.The results showed that the VEGF-A mRNA level in dox-group was significantly decreased compared with that in dox+group.The transcriptome sequencing data of the two groups of mice revealed a total of 1282 differential genes,including 803 up-regulated genes and 479 down-regulated genes.GO and KEGG enrichment analysis of differential genes showed that differential genes were mainly involved in T cell activation,adipocyte differentiation and thermogenesis,and were mainly located in the extracellular matrix and the outer part of the plasma membrane,and were enriched in the PI3K-AKT signaling pathway.Therefore,we concluded that inhibiting the expression of VEGF-A in mice can promote the up-regulation of EPO expression,thus affecting the level expression of genes related to the PI3K-AKT signaling pathway.

关 键 词：血管内皮生长因子-A 促红细胞生成素 RNA测序 

分 类 号：Q462[生物学—生理学]