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变应性鼻炎致病基因及上游调控因子的鉴定

Identification of pathogenic genes and upstream regulators in allergic rhinitis.

作者信息

Lei Yanhua, Guo Ping, An Jun, Guo Chao, Lu Fengxiang, Liu Minglei

机构信息

Department of Otolaryngology, Head and Neck Surgery, The First People's Hospital of Jining, China.

Department of Anesthesiology, The First People's Hospital of Jining, China.

出版信息

Int J Pediatr Otorhinolaryngol. 2018 Dec;115:97-103. doi: 10.1016/j.ijporl.2018.09.005. Epub 2018 Sep 19.

Abstract

BACKGROUND

Allergic rhinitis (AR) is the main cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AR.

METHODS

To screen pathogenic genes of AR, an integrated analysis was performed by using the microarray datasets in AR derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AR-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AR. Electronic validation was performed to verify the DEGs obtained by integrated analysis.

RESULTS

From two GEO datasets obtained, we identified 793 DEGs (460 up-regulated and 333 down-regulated genes) between AR and normal control (NC). After GO and KEGG analysis, chronic inflammatory response and MAPK signaling pathway were significantly enriched pathways for DEGs. The expression of 6 genes (CLC, CST1, CRTAM, ILK, STAT1, and POSTN) was detected. The 6 genes in GEO: GSE51392 dataset played the same pattern with that in our integrated analysis.

CONCLUSIONS

The dysregulation of 3 genes (CST1, CLC and STAT1) may be involved in the pathogenesis of AR. AP-1 was associated with AR by regulating CST1 and CLC. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AR.

摘要

背景

变应性鼻炎(AR)是老年人不可逆失明的主要原因。我们的研究旨在确定AR中的关键基因和上游调节因子。

方法

为筛选AR的致病基因,利用来自基因表达综合数据库(GEO)中AR的微阵列数据集进行综合分析。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析进一步发现差异表达基因(DEG)的功能注释和潜在途径。我们构建了AR特异性转录调控网络,以寻找靶向AR中DEG的关键转录因子(TF)。进行电子验证以验证通过综合分析获得的DEG。

结果

从获得的两个GEO数据集中,我们鉴定出AR与正常对照(NC)之间有793个DEG(460个上调基因和333个下调基因)。经过GO和KEGG分析,慢性炎症反应和丝裂原活化蛋白激酶(MAPK)信号通路是DEG显著富集的途径。检测了6个基因(CLC、CST1、CRTAM、ILK、STAT1和POSTN)的表达。GEO:GSE51392数据集中的6个基因与我们的综合分析呈现相同模式。

结论

3个基因(CST1、CLC和STAT1)的失调可能参与AR的发病机制。活化蛋白-1(AP-1)通过调节CST1和CLC与AR相关。我们的发现有助于开发新的潜在生物标志物,揭示潜在发病机制,并进一步为AR提出新的治疗靶点。

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