{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:28:37Z","timestamp":1790270917616,"version":"4.1.0"},"reference-count":38,"publisher":"BMJ","issue":"1","funder":[{"name":"Research initiation grant from CIBERES"},{"name":"Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Madrid, Spain, and Fondos FEDER \"Una Manera de hacer Europa\"."},{"name":"Merit Award. United States Department of Veterans Affairs Biomedical Laboratory R&D (BLRD) Service."},{"name":"Miguel Servet Fellowship. Instituto de Salud Carlos III"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>The acute respiratory distress syndrome (ARDS) is characterized by protein-rich oedema in the alveolar spaces, a feature in which Fas-mediated apoptosis of the alveolar epithelium has been involved.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold>To determine whether Fas activation increases protein permeability by mechanisms involving disruption of the paracellular tight junction (TJ) proteins in the pulmonary alveoli.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>Protein permeability and the expression of TJ proteins were assessed in vivo in wild-type and Fas-deficient lpr mice 16 hours after the intratracheal instillation of recombinant human soluble Fas ligand (rh-sFasL), and at different time points in vitro in human pulmonary alveolar epithelial cells (HPAEpiC) exposed to rh-sFasL<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>Activation of the Fas pathway increased protein permeability in mouse lungs and altered the expression of the TJ proteins occludin and zonula occludens-1 in the alveolar\u2013capillary membrane in vivo and in human alveolar epithelial cell monolayers in vitro. Blockade of caspase-3, but not inhibition of tyrosine kinase dependent pathways, prevented the alterations in TJ protein expression and permeability induced by the Fas\/FasL system in human alveolar cell monolayers in vitro. We also observed that both the Fas-induced increase of protein permeability and disruption of TJ proteins occurred before cell death could be detected in the cell monolayers in vitro.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold>Targeting caspase pathways could prevent the disruption of TJs and reduce the formation of lung oedema in the early stages of ARDS.<\/jats:p>","DOI":"10.1136\/thoraxjnl-2018-211535","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T16:15:30Z","timestamp":1541088930000},"page":"69-82","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Fas activation alters tight junction proteins in acute lung 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