Changing Cellular Phenotypes Induced by Soluble Factors from Dengue Virus Infection

Dengue is a viral disease and a global public health problem. It can be presented as complicated (Severe Dengue, SD), characterized by endothelial dysfunction, for which there is only palliative treatment. It has been considered that soluble factors in conditioned media from Dengue virus infection (CMDV) can induce a cellular plasticity event, such as the endothelial-mesenchymal transition (EndMT), and influence the dysfunction. The objectives of this work are to determine if CMDV induces cellular phenotypical changes and if it promotes endothelial permeability. Endothelial microvasculature cells were exposed to CMDV for 48 to 120 hours, and alterations in endothelial permeability (TEER), morphology (confocal laser microscopy and atomic force microscopy), and the expression of markers associated with EndMT (In-cell western and RNA-seq bulk) were evaluated. CMDV was found to have a biphasic effect on cells: in the acute phase, they induce temporary alterations of the ECM and cytoskeleton, generating a migratory phenotype, increasing the expression of mesenchymal proteins (SNAIL, TWIST1, N-Cad), and inducing a temporary proinflammatory response followed by an endothelial repair response phase. This dynamic behavior can be model in an asynchronous Boolean network that allows elucidating the mechanisms associated with both cellular responses caused by CMDV and it highlights possible therapeutic targets such as IL-6 and FN1, which can be tested to prevent endothelial dysfunction. The results show that soluble CMDV factors induce a transient EndMT-like state and influence endothelial dysfunction, which can be modeled to detail the mechanisms involved in it and to identify potential therapeutic targets.

• Autores: Alfaro García, Jenny Paola
• Tipo de recurso: Doctoral thesis
• Fecha de publicación: 2025
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/47470
• Acceso en línea: https://hdl.handle.net/10495/47470
• Palabra clave: Cell plasticity; Plasticidad de la célula; Dengue; Endothelial cells; Células endoteliales; Endothelial-mesenchymal transition; Transición endotelial-mesenquimatosa; Endothelial dysfunction; Soluble factors; https://id.nlm.nih.gov/mesh/D000066670; https://id.nlm.nih.gov/mesh/D003715; https://id.nlm.nih.gov/mesh/D042783; https://id.nlm.nih.gov/mesh/D000096382; ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
• Rights: embargoedAccess
• License: http://creativecommons.org/licenses/by-nc-sa/4.0/