Iguaracy Pinheiro-de-Sousa, Miriam Helena Fonseca-Alaniz, Girolamo Giudice, Iuri Cordeiro Valadão, Silvestre Massimo Modestia, Sarah Viana Mattioli, Ricardo Rosa Junior, Lykourgos-Panagiotis Zalmas, Yun Fang, Evangelia Petsalaki, José Eduardo Krieger
{"title":"综合系统生物学方法确定内皮功能障碍的基因靶标。","authors":"Iguaracy Pinheiro-de-Sousa, Miriam Helena Fonseca-Alaniz, Girolamo Giudice, Iuri Cordeiro Valadão, Silvestre Massimo Modestia, Sarah Viana Mattioli, Ricardo Rosa Junior, Lykourgos-Panagiotis Zalmas, Yun Fang, Evangelia Petsalaki, José Eduardo Krieger","doi":"10.15252/msb.202211462","DOIUrl":null,"url":null,"abstract":"<p><p>Endothelial 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.</p>","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":null,"pages":null},"PeriodicalIF":8.5000,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10698507/pdf/","citationCount":"0","resultStr":"{\"title\":\"Integrated systems biology approach identifies gene targets for endothelial dysfunction.\",\"authors\":\"Iguaracy Pinheiro-de-Sousa, Miriam Helena Fonseca-Alaniz, Girolamo Giudice, Iuri Cordeiro Valadão, Silvestre Massimo Modestia, Sarah Viana Mattioli, Ricardo Rosa Junior, Lykourgos-Panagiotis Zalmas, Yun Fang, Evangelia Petsalaki, José Eduardo Krieger\",\"doi\":\"10.15252/msb.202211462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Endothelial 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.</p>\",\"PeriodicalId\":18906,\"journal\":{\"name\":\"Molecular Systems Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2023-12-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10698507/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Systems Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.15252/msb.202211462\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Systems Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.15252/msb.202211462","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Integrated systems biology approach identifies gene targets for endothelial dysfunction.
Endothelial 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.
期刊介绍:
Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems.
Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.