Integrated systems biology approach identifies gene targets for endothelial dysfunction

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorEuropean Bioinformatics Institute-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorWellcome Trust Sanger Institute-
Autor(es): dc.contributorOpen Targets-
Autor(es): dc.contributorUniversity of Chicago-
Autor(es): dc.creatorPinheiro-de-Sousa, Iguaracy-
Autor(es): dc.creatorFonseca-Alaniz, Miriam Helena-
Autor(es): dc.creatorGiudice, Girolamo-
Autor(es): dc.creatorValadão, Iuri Cordeiro-
Autor(es): dc.creatorModestia, Silvestre Massimo-
Autor(es): dc.creatorMattioli, Sarah Viana-
Autor(es): dc.creatorJunior, Ricardo Rosa-
Autor(es): dc.creatorZalmas, Lykourgos-Panagiotis-
Autor(es): dc.creatorFang, Yun-
Autor(es): dc.creatorPetsalaki, Evangelia-
Autor(es): dc.creatorKrieger, José Eduardo-
Data de aceite: dc.date.accessioned2025-08-21T18:52:54Z-
Data de disponibilização: dc.date.available2025-08-21T18:52:54Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-12-05-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.15252/msb.202211462-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/298942-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/298942-
Descrição: dc.descriptionEndothelial dysfunction (ED) is critical in the development and progression of cardiovascular (CV) disorders, yet effective therapeutic targets for ED remain elusive due to limited understanding of its underlying molecular mechanisms. To address this gap, we employed a systems biology approach to identify potential targets for ED. Our study combined multi omics data integration, with siRNA screening, high content imaging and network analysis to prioritise key ED genes and identify a pro- and anti-ED network. We found 26 genes that, upon silencing, exacerbated the ED phenotypes tested, and network propagation identified a pro-ED network enriched in functions associated with inflammatory responses. Conversely, 31 genes ameliorated ED phenotypes, pointing to potential ED targets, and the respective anti-ED network was enriched in hypoxia, angiogenesis and cancer-related processes. An independent screen with 17 drugs found general agreement with the trends from our siRNA screen and further highlighted DUSP1, IL6 and CCL2 as potential candidates for targeting ED. Overall, our results demonstrate the potential of integrated system biology approaches in discovering disease-specific candidate drug targets for endothelial dysfunction.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionLaboratory of Genetics and Molecular Cardiology Heart Institute (InCor)/University of São Paulo Medical School-
Descrição: dc.descriptionEuropean Molecular Biology Laboratory European Bioinformatics Institute-
Descrição: dc.descriptionDepartment of Biophysics and Pharmacology Institute of Biosciences of Botucatu Universidade Estadual Paulista-
Descrição: dc.descriptionWellcome Trust Sanger Institute, Wellcome Trust Genome Campus-
Descrição: dc.descriptionOpen Targets, Wellcome Genome Campus-
Descrição: dc.descriptionDepartment of Medicine University of Chicago-
Descrição: dc.descriptionDepartment of Biophysics and Pharmacology Institute of Biosciences of Botucatu Universidade Estadual Paulista-
Descrição: dc.descriptionCNPq: 309179/2013-0-
Descrição: dc.descriptionCAPES: CAPES 88882.328126/2019-01-
Idioma: dc.languageen-
Relação: dc.relationMolecular Systems Biology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectdata integration-
Palavras-chave: dc.subjectdrug targets-
Palavras-chave: dc.subjectendothelial dysfunction-
Palavras-chave: dc.subjectnetwork analysis-
Palavras-chave: dc.subjectsystems biology-
Título: dc.titleIntegrated systems biology approach identifies gene targets for endothelial dysfunction-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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