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通过生物信息学分析预测与高血压相关的标记基因。

Prediction of marker genes associated with hypertension by bioinformatics analyses.

作者信息

Gao Yuan, Qi Guo-Xian, Jia Zhi-Mei, Sun Ying-Xian

机构信息

Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

出版信息

Int J Mol Med. 2017 Jul;40(1):137-145. doi: 10.3892/ijmm.2017.3000. Epub 2017 May 25.

Abstract

This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses. A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed. In total, 411 DEGs were identified between the HF and NF groups, and 418 DEGs were identified between the HM and NM groups. The upregulated DEGs in the HF and HM groups were enriched in 9 GO terms, including oxidation reduction, such as cytochrome P450, family 4, subfamily b, polypeptide 1 (Cyp4b1) and cytochrome P450, family 4, subfamily a, polypeptide 31 Cyp4a31). The downregulated DEGs were mainly enriched in GO terms related to hormone metabolic processes. In the PPI network, cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) had the highest degree in all 3 analysis methods in the HF group. Additionally, 4 TFs were indentified from the 2 groups of data, including sterol regulatory element binding transcription factor 1 (Srebf1), estrogen receptor 1 (Esr1), retinoid X receptor gamma (Rxrg) and peroxisome proliferator-activated receptor gamma (Pparg). The intersection genes were mainly enriched in GO terms related to the extracellular region. On the whole, our data indicate that the DEGs, Cyp4b1, Cyp4a31 and Loxl2, and the TFs, Esr1, Pparg and Rxrg, are associated with the progression of hypertension, and may thus serve as potential therapeutic targets in this disease.

摘要

本研究旨在通过生物信息学分析探索与高血压相关的潜在标志物基因。下载了一个基因表达谱(GSE54015)。分析了正常血压女性(NF)与高血压女性(HF)组之间以及正常血压男性(NM)与高血压男性(HM)组之间的差异表达基因(DEG)。进行了基因本体论(GO)和通路富集分析,随后构建了蛋白质 - 蛋白质相互作用(PPI)网络。然后分析了转录因子(TF)以及HF和HM组之间的共同DEG。HF组和NF组之间共鉴定出411个DEG,HM组和NM组之间共鉴定出418个DEG。HF组和HM组中上调的DEG在9个GO术语中富集,包括氧化还原,如细胞色素P450 4家族b亚家族多肽1(Cyp4b1)和细胞色素P450 4家族a亚家族多肽31(Cyp4a31)。下调的DEG主要富集在与激素代谢过程相关的GO术语中。在PPI网络中,细胞色素P450 2家族e亚家族多肽1(Cyp2e1)在HF组的所有3种分析方法中度数最高。此外,从两组数据中鉴定出4个TF,包括甾醇调节元件结合转录因子1(Srebf1)、雌激素受体1(Esr1)、视黄酸X受体γ(Rxrg)和过氧化物酶体增殖物激活受体γ(Pparg)。交集基因主要富集在与细胞外区域相关的GO术语中。总体而言,我们的数据表明,DEG(Cyp4b1、Cyp4a31和Loxl2)以及TF(Esr1、Pparg和Rxrg)与高血压的进展相关,因此可能作为该疾病的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/223c/5466388/cca727b417b6/IJMM-40-01-0137-g00.jpg

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