Identification of key genes and pathways in scleral extracellular matrix remodeling in glaucoma: Potential therapeutic agents discovered using bioinformatics analysis.
Identification of key genes and pathways in scleral extracellular matrix remodeling in glaucoma: Potential therapeutic agents discovered using bioinformatics analysis.
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DOI：
10.7150/ijms.52846
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发表时间：
2021
影响因子：
3.6
通讯作者：
Qian S
中科院分区：
文献类型：
--
作者：
Hu D;Jiang J;Lin Z;Zhang C;Moonasar N;Qian S
背景：青光眼是导致不可逆性失明的主要原因。巩膜细胞外基质（ECM）的重塑在青光眼的发生发展中起着重要作用。本研究的目的是通过生物信息学分析确定青光眼巩膜细胞外基质重塑的关键基因和途径，并探索潜在的青光眼治疗药物。研究方法：使用文本挖掘工具pubmed 2 ensembl检测与青光眼、巩膜和ECM重塑相关的基因，并使用GeneCodis程序分配基因本体论（GO）生物过程术语和京都基因和基因组百科全书（KEGG）途径。通过STRING构建蛋白质-蛋白质相互作用（PPI）网络并在Cytoscape中可视化，使用分子复合物检测（MCODE）插件进行模块分析，并使用注释、可视化和集成发现数据库（大卫）平台进行基因模块的GO和KEGG分析。选择聚集在显著模块中的基因作为核心基因，并使用CCLGO和CCLPedia可视化核心基因的功能和途径。最后，利用药物-基因相互作用数据库研究核心基因的药物-基因相互作用，寻找治疗青光眼的候选药物。结果：我们通过文本挖掘确定了125个与“青光眼”、“巩膜”和“ECM重塑”相关的基因。基因功能富集分析产生了30个富集的GO术语和20个相关的KEGG途径。构建了一个包含60个节点、249条边的PPI网络，并使用MCODE获得了3个基因模块。我们选择了聚集在模块1中的13个基因作为核心候选基因，这些基因主要与ECM降解和细胞增殖和分裂相关。HIF-1信号通路、FOXO信号通路、PI 3 K-Akt信号通路和TGFB信号通路在细胞中富集。我们发现13个选定基因中的11个可以被26种现有药物靶向。结论：结果表明，VEGFA、TGFB 1、TGFB 2、TGFB 3、IGF 2、IGF 1、EGF、FN 1、KNG 1、TIMP 1、SERPINE 1、THBS 1和VWF可能是参与巩膜ECM重塑的关键基因。此外，26种药物被确定为青光眼治疗和管理的潜在治疗药物。
Background: Glaucoma is a leading cause of irreversible blindness. Remodeling of the scleral extracellular matrix (ECM) plays an important role in the development of glaucoma. The aim of this study was to identify the key genes and pathways for the ECM remodeling of sclera in glaucoma by bioinformatics analysis and to explore potential therapeutic agents for glaucoma management. Methods: Genes associated with glaucoma, sclera and ECM remodeling were detected using the text mining tool pubmed2ensembl, and assigned Gene Ontology (GO) biological process terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the GeneCodis program. A protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape, module analysis was performed using the Molecular Complex Detection (MCODE) plugin, and GO and KEGG analyses of the gene modules were performed using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The genes that clustered in the significant module were selected as core genes, and functions and pathways of the core genes were visualized using ClueGO and CluePedia. Lastly, the drug-gene interaction database was used to explore drug-gene interactions of the core genes to find drug candidates for glaucoma. Results: We identified 125 genes common to “Glaucoma”, “Sclera”, and “ECM remodeling” by text mining. Gene functional enrichment analysis yielded 30 enriched GO terms and 20 associated KEGG pathways. A PPI network that included 60 nodes with 249 edges was constructed, and three gene modules were obtained using the MCODE. We selected 13 genes that clustered in module 1 as core candidate genes that were associated mainly with ECM degradation and cell proliferation and division. The HIF-1 signaling pathway, FOXO signaling pathway, PI3K-Akt signaling pathway and TGFB signaling pathway were found to be enriched. We found that 11 of the 13 selected genes could be targeted by 26 existing drugs. Conclusions: The results showed that VEGFA, TGFB1, TGFB2, TGFB3, IGF2, IGF1, EGF, FN1, KNG1, TIMP1, SERPINE1, THBS1, and VWF were potential key genes involved to scleral ECM remodeling. Furthermore, 26 drugs were identified as potential therapeutic agents for glaucoma treatment and management.
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影响因子：
3.9
作者：
Ebneter, A.;Wagels, B.;Zinkernagel, M. S.
通讯作者：
Zinkernagel, M. S.
影响因子：
4.8
作者：
Duncan, MR;Frazier, KS;Grotendorst, GR
通讯作者：
Grotendorst, GR
卡维地洛可能通过 VEGF-Src-ERK 信号通路抑制血管生成，从而减轻肝硬化
影响因子：
4.3
作者：
Ding, Qian;Tian, Xiang-Guo;Zhang, Chun-Qing
通讯作者：
Zhang, Chun-Qing
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
DOI：
10.3904/kjim.2014.29.2.176
发表时间：
2014-03
期刊：
The Korean journal of internal medicine
影响因子：
--
作者：
Lee JH;Oh MH;Park JS;Na GJ;Gil HW;Yang JO;Lee EY;Hong SY
通讯作者：
Hong SY