{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:53:45Z","timestamp":1785524025524,"version":"3.56.0"},"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia","award":["CTO 917-2019"],"award-info":[{"award-number":["CTO 917-2019"]}]},{"DOI":"10.13039\/501100005278","name":"Universidad de Antioquia","doi-asserted-by":"publisher","award":["CODI-2020-34137"],"award-info":[{"award-number":["CODI-2020-34137"]}],"id":[{"id":"10.13039\/501100005278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-153018NB-I00"],"award-info":[{"award-number":["PID2023-153018NB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["ECRIN-M3"],"award-info":[{"award-number":["ECRIN-M3"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Dengue virus (DENV) represents a growing global health challenge with billions of people at risk. Severe Dengue (SD), a complication of DENV infection that involves generalized hemorrhage, is driven, at least in part, by endothelial dysfunction. Endothelial dysfunction refers to increased permeability due to inflammation, mechanical injury and\/or modification of the genetic program of endothelial cells. Previous work showed that exposure of endothelial cells to conditioned media from DENV-infected cells (CMDV) increased permeability and cellular stiffness, repressed endothelial markers and induced mesenchymal genes. However, the generality, extent, mechanism and ultimate impact of these events in the onset of SD remain elusive. Here, we integrate analysis from in vitro treatment of endothelial cells with media containing UV-inactivated DENV with computational modeling to investigate the key features of CMDV-induced endothelial alterations and their potential impact on endothelial dysfunction. We found that CMDV increased\n                    <jats:italic>SNA1<\/jats:italic>\n                    and\n                    <jats:italic>CDH2<\/jats:italic>\n                    expression, while suppressing endothelial genes\n                    <jats:italic>OCLN<\/jats:italic>\n                    and\n                    <jats:italic>CDH5<\/jats:italic>\n                    . Global transcriptomics analysis revealed that CMDV triggered a transient pro-inflammatory response, followed by induction of selected tissue repair genes and matrix remodeling. A non-directed asynchronous network model (NDAM-CMDV) identified IL6 and FN1 as central nodes of DENV-induced endothelial trans-differentiation, providing new molecular insights that predict the evolution of the disease and identify potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0354877","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:30:56Z","timestamp":1785519056000},"page":"e0354877","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular analysis and computational modeling reveal temporally separable responses triggered by DENV-induced soluble factors in endothelial cells"],"prefix":"10.1371","volume":"21","author":[{"given":"Jenny Paola","family":"Alfaro-Garc\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julieta Mar\u00eda","family":"Ram\u00edrez-Mej\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rojas-Estevez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Alejandro","family":"\u00c1lvarez-D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-1587","authenticated-orcid":true,"given":"Geysson Javier","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto","family":"Orozco-Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris Anghelo","family":"Rodr\u00edguez-Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Gallego-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-3220","authenticated-orcid":true,"given":"Miguel","family":"Vicente-Manzanares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"8","key":"pone.0354877.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001760","article-title":"Refining the global spatial limits of dengue virus transmission by evidence-based consensus","volume":"6","author":"OJ Brady","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"pone.0354877.ref002","doi-asserted-by":"crossref","first-page":"100107","DOI":"10.1016\/j.microb.2024.100107","article-title":"Global re-emergence of dengue fever: The need for a rapid response and surveillance","volume":"4","author":"OC Akinsulie","year":"2024","journal-title":"The Microbe"},{"key":"pone.0354877.ref003","unstructured":"Pan American Health Organization, World Health Organization. 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