A Bioinformatics Perspective on the Links Between Tetraspanin-Enriched Microdomains and Cardiovascular Pathophysiology.
A Bioinformatics Perspective on the Links Between Tetraspanin-Enriched Microdomains and Cardiovascular Pathophysiology.
复制标题
DOI：
10.3389/fcvm.2021.630471
复制
发表时间：
2021
影响因子：
3.6
通讯作者：
Zhang XA
中科院分区：
文献类型：
--
作者：
Sun G;Chen J;Ding Y;Wren JD;Xu F;Lu L;Wang Y;Wang DW;Zhang XA
背景：四跨膜蛋白和整联蛋白是不可或缺的膜蛋白。四跨膜蛋白与整联蛋白相互作用，以称为四跨膜蛋白富集微结构域（TEM）的膜结构域的形式调节粘附、迁移、增殖和信号传导的动力学。TEM还含有其他细胞粘附蛋白，如免疫球蛋白超家族（IgSF）蛋白和封闭蛋白。这些TEM蛋白的心血管功能已经显现，但仍有待进一步揭示。目的：本研究的目的是使用生物信息学工具和数据库探索这些TEM蛋白在心血管系统中的作用，并强调可能与心血管生理和病理功能相关的TEM蛋白。方法：对于人体样本，使用三个数据库-GTEx，NCBI-dbGaP和NCBI-GEO-进行分析。dbGaP数据库用于GWAS分析以确定靶基因与人类表型之间的关联。GEO是一个NCBI公共存储库，用于存档基因组学数据。GTEx用于分析组织特异性mRNA表达水平和eQTL。对于小鼠样品，使用GeneNetwork来发现小鼠中表达水平的基因-表型相关性和基因-基因相关性。心血管数据的分析是本研究的重点。结果：ITGA 8、Cd 151等整合素和四跨膜蛋白在人心血管系统中高表达。TEM成分与人类多种心血管病理生理事件相关。GWAS和GEO分析表明，人Cd 82和ITGA 9与血压相关。来自小鼠的数据还表明，各种心血管表型与整合素和四跨膜蛋白相关。例如，Cd 82和ITGA 9再次与小鼠的血压相关。结论：ITGA 9与两种动物的血压相关。KEGG分析还将ITGA 9与代谢和MAPK信号通路联系起来。这项工作提供了一个例子，使用跨不同物种的综合生物信息学方法，以确定结构和/或功能相关的分子与某些类别的疾病的连接。
Background: Tetraspanins and integrins are integral membrane proteins. Tetraspanins interact with integrins to modulate the dynamics of adhesion, migration, proliferation, and signaling in the form of membrane domains called tetraspanin-enriched microdomains (TEMs). TEMs also contain other cell adhesion proteins like immunoglobulin superfamily (IgSF) proteins and claudins. Cardiovascular functions of these TEM proteins have emerged and remain to be further revealed. Objectives: The aims of this study are to explore the roles of these TEM proteins in the cardiovascular system using bioinformatics tools and databases and to highlight the TEM proteins that may functionally associate with cardiovascular physiology and pathology. Methods: For human samples, three databases—GTEx, NCBI-dbGaP, and NCBI-GEO—were used for the analyses. The dbGaP database was used for GWAS analysis to determine the association between target genes and human phenotypes. GEO is an NCBI public repository that archives genomics data. GTEx was used for the analyses of tissue-specific mRNA expression levels and eQTL. For murine samples, GeneNetwork was used to find gene–phenotype correlations and gene–gene correlations of expression levels in mice. The analysis of cardiovascular data was the focus of this study. Results: Some integrins and tetraspanins, such as ITGA8 and Cd151, are highly expressed in the human cardiovascular system. TEM components are associated with multiple cardiovascular pathophysiological events in humans. GWAS and GEO analyses showed that human Cd82 and ITGA9 are associated with blood pressure. Data from mice also suggest that various cardiovascular phenotypes are correlated with integrins and tetraspanins. For instance, Cd82 and ITGA9, again, have correlations with blood pressure in mice. Conclusion: ITGA9 is related to blood pressure in both species. KEGG analysis also linked ITGA9 to metabolism and MAPK signaling pathway. This work provides an example of using integrated bioinformatics approaches across different species to identify the connections of structurally and/or functionally related molecules to certain categories of diseases.
登录
查看更多内容
影响因子：
4
作者：
Bridgewater, Rebecca E.;Norman, Jim C.;Caswell, Patrick T.
通讯作者：
Caswell, Patrick T.
影响因子：
4.6
作者：
Chu, Liang-Hui;Vijay, Chaitanya G.;Popel, Aleksander S.
通讯作者：
Popel, Aleksander S.
DOI：
10.1007/s00018-017-2490-4
发表时间：
2017-06
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Finney AC;Stokes KY;Pattillo CB;Orr AW
通讯作者：
Orr AW
影响因子：
7.5
作者：
Delon, Isabelle;Brown, Nicholas H.
通讯作者：
Brown, Nicholas H.
影响因子：
64.8
作者：
Dekel, E;Alon, U
通讯作者：
Alon, U