摘要
为了寻找特发性肺纤维化(IPF)的潜在治疗靶点,从GEO获取IPF基因芯片数据,用R分析差异表达基因和通路;用STRING和Cytoscape筛选枢纽(HUB)基因;RNA-Seq和单细胞数据验证,肺纤维化小鼠实验验证,筛选具有相关性的基因,分析潜在通路.结果显示:基因芯片数据集GSE10667、GSE53845、GSE48149共116例样本,差异基因132个,主要富集在细胞外基质、胶原等通路.STRING和Cytoscape筛选HUB基因,主要为 COL1A1、CXCL12、LEPREL1 等基因,其中 LEPREL1 表达显著下调(GSE10667,Padj=0.000 96;GSE53845,Padj=0.000 104 8;GSE48149,Padj=0.015 17).LEPREL1 在 RNA-Seq 数据集 GSE92592(Padj=0.028 8)、GSE83717(Padj=0.006 268)、GSE150910(Padj=1.952 8e-30)中均显著下调;在单细胞数据(GSE135893)中主要在AT2细胞中表达并有下调趋势;在肺纤维化小鼠的RT-qPCR和IHC中也表达显著下调.差异表达基因中有81个与LEPREL1具相关性的基因,主要与细胞黏附、钙离子、胶原形成、Wnt等通路相关.IPF的差异基因主要富集在胶原和细胞外基质通路,且AT2细胞中下调的LEPREL1可能是其潜在治疗靶点.
Abstract
To find potential therapeutic target for idiopathic pulmonary fibrosis(IPF),GEO was used to get gene microarray datas,R was used to analyse differentially expressed genes and pathways;Strings and Cytoscape were used to screen HUB genes(key genes);RNA-seq and single cell data were as data validation,lung fibrosis mice were as experiment validation.The results showed that gene microarray datasets GSE10667,GSE53845,GSE48149 have 116 samples and 132 differential genes,pathways were enriched in extracellular matrix,collagen and so on.COL1A1,CXCL12,LEPREL1 and other genes were screened as HUB genes by STRING and Cytoscape.Among HUB genes,LEPREL1 expression was significantly down-regulated(GSE10667,Padj=0.000 96;GSE53845,Padj=0.000 104 8;GSE48149,Padj=0.015 17).In the RNA-Seq datasets GSE92592(Padj=0.028 8),GSE83717(Padj=0.006 268),GSE150910(Padj=1.952 8E-30)LEPREL1 were also significantly down-regulated;in the single cell data(GSE135893)LEPREL1 was mainly expressed in AT2 cells and tended to be down-regulated;it was also significantly down-regulated in RT-qPCR and 1HC in lung fibrosis mice.81 differentially expressed genes were associated with LEPREL1,mainly enriched in cell adhesion,calcium,collagen and Wnt pathways.The differential genes in IPF are mainly enriched in collagen and extracellular matrix pathways,and LEPREL1,which is down-regulated in AT2 cells,may be a potential therapeutic target for IPF.
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