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使用生物信息学分析鉴定白色脂肪细胞胰岛素抵抗的生物标志物、途径和潜在治疗药物。

Identification of biomarkers, pathways and potential therapeutic agents for white adipocyte insulin resistance using bioinformatics analysis.

机构信息

a Department of Pathology and Pathophysiology, Wuhan University School of Basic Medical Sciences , Wuhan , China.

b Hubei Provincial Key Laboratory of Developmentally Originated Disease , Wuhan , China.

出版信息

Adipocyte. 2019 Dec;8(1):318-329. doi: 10.1080/21623945.2019.1649578.

Abstract

For the better understanding of insulin resistance (IR), the molecular biomarkers in IR white adipocytes and its potential mechanism, we downloaded two mRNA expression profiles from Gene Expression Omnibus (GEO). The white adipocyte samples in two databases were collected from the human omental adipose tissue of IR obese (IRO) subjects and insulin-sensitive obese (ISO) subjects, respectively. We identified 86 differentially expressed genes (DEGs) between the IRO and ISO subjects using limma package in R software. Gene Set Enrichment Analysis (GSEA) provided evidence that the most gene sets enriched in kidney mesenchyme development in the ISO subjects, as compared with the IRO subjects. The Gene Ontology (GO) analysis indicated that the most significantly enriched in cellular response to interferon-gamma. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were most significantly enriched in cytokine-cytokine receptor interaction. Protein-Protein Interaction (PPI) network was performed with the STRING, and the top 10 hub genes were identified with the Cytohubba. CMap analysis found several small molecular compounds to reverse the altered DEGs, including dropropizine, aceclofenac, melatonin, and so on. Our outputs could empower the novel potential targets to treat omental white adipocyte insulin resistance, diabetes, and diabetes-related diseases.

摘要

为了更好地理解胰岛素抵抗(IR)、IR 白色脂肪细胞中的分子生物标志物及其潜在机制,我们从基因表达综合数据库(GEO)下载了两个 mRNA 表达谱。这两个数据库中的白色脂肪细胞样本分别取自胰岛素抵抗肥胖(IRO)和胰岛素敏感肥胖(ISO)受试者的人网膜脂肪组织。我们使用 R 软件中的 limma 包鉴定出 IRO 和 ISO 受试者之间的 86 个差异表达基因(DEG)。基因集富集分析(GSEA)提供的证据表明,与 IRO 受试者相比,ISO 受试者中肾脏间质发育的基因集最丰富。基因本体论(GO)分析表明,细胞对干扰素-γ的反应最显著富集。京都基因与基因组百科全书(KEGG)通路分析表明,差异表达基因最显著富集于细胞因子-细胞因子受体相互作用。我们使用 STRING 进行蛋白质-蛋白质相互作用(PPI)网络分析,并使用 Cytohubba 鉴定出前 10 个枢纽基因。CMap 分析发现了几种小分子化合物可以逆转改变的 DEG,包括喷托维林、双氯芬酸、褪黑素等。我们的研究结果为治疗网膜白色脂肪细胞胰岛素抵抗、糖尿病及其相关疾病提供了新的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/647b/6768254/a6a99be3e0f5/kadi-08-01-1649578-g001.jpg

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