Bioinformatics analysis of fibroblasts exposed to TGF‑β at the early proliferation phase of wound repair.
Bioinformatics analysis of fibroblasts exposed to TGF‑β at the early proliferation phase of wound repair.
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在伤口修复的早期增殖阶段暴露于TGF -β的成纤维细胞的生物信息学分析。
DOI：
10.3892/mmr.2017.7619
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Mi B;Liu G;Zhou W;Lv H;Zha K;Liu Y;Wu Q;Liu J
本研究的目的是确定创面修复早期增殖阶段的基因特征，以及转化生长因子-β对成纤维细胞的影响，并揭示其可能的机制。从GEO数据库中获得GSE79621和GSE27165的基因表达谱。用Morpheus鉴定差异表达基因(DEG)，用维恩图选择共表达的DEG。使用注释、可视化和集成发现数据库(David)在线工具进行DEGS的基因本体论(GO)功能和京都基因和基因组百科全书(KEGG)途径丰富分析。用Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络。利用MCODE算法将PPI交互网络划分为多个子网络，并利用David软件对上层模块的功能进行了分析。结果显示，上调的degs在生物学过程中显著丰富，包括Arp2/3复合体介导的肌动蛋白成核、透明质酸电缆组装的正调节、嘌呤核苷酸碱基的生物合成过程、一磷酸肌苷的生物合成过程、对上皮细胞增殖的正调控，而下调的degs则富集于血压调节、细胞增殖负调控、骨化、基因表达负调控和I型干扰素信号通路。KEGG途径分析表明，上调的degs在志贺氏菌病、致病性大肠埃希氏菌感染、丝裂原活化蛋白激酶信号通路、RAS信号通路和细菌对上皮细胞的侵袭中均有丰富的表达。下调的DEGS主要集中在系统性红斑狼疮、溶酶体、花生四烯酸代谢、甲状腺癌和同种异体排斥反应中。从PPI网络中确定了前10个HUB基因。顶端模块分析表明，所包含的基因涉及离子通道、神经活性配体-受体相互作用途径、嘌呤代谢和肠道免疫网络中的IgA产生途径。功能分析表明，转化生长因子-β在创面修复的早期增殖阶段可能促进成纤维细胞的迁移和增殖，并对微生物具有保护作用。此外，这些结果可能为慢性创面修复提供参考。
The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF-β on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co-expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Protein-protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. PPI interaction network was divided into subnetworks using the MCODE algorithm and the function of the top one module was analyzed using DAVID. The results revealed that upregulated DEGs were significantly enriched in biological process, including the Arp2/3 complex-mediated actin nucleation, positive regulation of hyaluronan cable assembly, purine nucleobase biosynthetic process, de novo inosine monophosphate biosynthetic process, positive regulation of epithelial cell proliferation, whereas the downregulated DEGs were enriched in the regulation of blood pressure, negative regulation of cell proliferation, ossification, negative regulation of gene expression and type I interferon signaling pathway. KEGG pathway analysis showed that the upregulated DEGs were enriched in shigellosis, pathogenic Escherichia coli infection, the mitogen-activated protein kinase signaling pathway, Ras signaling pathway and bacterial invasion of epithelial cells. The downregulated DEGs were enriched in systemic lupus erythematosus, lysosome, arachidonic acid metabolism, thyroid cancer and allograft rejection. The top 10 hub genes were identified from the PPI network. The top module analysis revealed that the included genes were involved in ion channel, neuroactive ligand-receptor interaction pathway, purine metabolism and intestinal immune network for IgA production pathway. The functional analysis revealed that TGF-β may promote fibroblast migration and proliferation and defend against microorganisms at the early proliferation stage of wound repair. Furthermore, these results may provide references for chronic wound repair.
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影响因子：
4.9
作者：
Adachi T;Sakurai T;Kashida H;Mine H;Hagiwara S;Matsui S;Yoshida K;Nishida N;Watanabe T;Itoh K;Fujita J;Kudo M
通讯作者：
Kudo M
影响因子：
4.9
作者：
Agarwal SK;Wu M;Livingston CK;Parks DH;Mayes MD;Arnett FC;Tan FK
通讯作者：
Tan FK
影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
影响因子：
6.1
作者：
Baer ML;Colello RJ
通讯作者：
Colello RJ
影响因子：
3.7
作者：
Elgaaen, Bente Vilming;Olstad, Ole Kristoffer;Gautvik, Kaare M.
通讯作者：
Gautvik, Kaare M.