{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:53Z","timestamp":1783003913485,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lung injury and fibrosis involve a complex interplay between inflammation and coagulation, with tissue factor (TF\/CF\u2010III\/Thromboplastin\/CD142) acting as a crucial mediator. Despite its known role in initiating the extrinsic coagulation cascade, TF's contribution to fibrin deposition in lung injury remains underexplored. This study examines the dysregulation of the extrinsic coagulation cascade and its pathological implications in lung injury, contributing to the progression of pulmonary fibrosis (PF). Utilizing bleomycin (BLM), transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2), and TF models, we systematically investigate coagulation\u2010driven inflammatory responses in lung pathology. By integrating in\u00a0vitro (A549 and Beas2b epithelial cell models) and in\u00a0vivo (C57BL\/6 murine models) approaches, this study elucidates TF\u2010mediated molecular mechanisms driving inflammation, fibrin deposition, endothelial dysfunction, and fibrotic remodeling. Protein\u2010protein interaction (PPI) network analysis highlights functional associations between coagulation factors (CFs) and inflammatory mediators, reinforcing their involvement in lung homeostasis. Also, gene enrichment analysis identifies key biological processes, including coagulation, fibrinolysis, and immune activation, emphasizing their role in disease progression. In A549 and Beas2b epithelial cells, CF\u2010III, CF\u2010VII, and CF\u2010X expression increased significantly, with A549 cells exhibiting a heightened pro\u2010coagulant response. Elevated IL\u20106, TNF\u2010\u03b1, and IL\u20101\u03b2 levels suggest an inflammatory amplification tied to TF activation. Immunofluorescence analysis demonstrates marked TF upregulation and TNF\u2010\u03b1 activation, reinforcing the interplay between coagulation pathways and inflammatory cytokine signaling. Histological assessments (H&amp;E, and Masson Trichrome [MT] staining) in murine lung tissues confirm fibrotic and inflammatory changes, reinforcing TF's pathogenic role. Our findings establish TF as a key molecular driver of thrombo\u2010inflammatory lung injury, providing potential therapeutic targets to mitigate fibrosis and improve patient outcomes.<\/jats:p>","DOI":"10.1002\/iub.70060","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T07:10:42Z","timestamp":1758352242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue Factor Driven Coagulation and Inflammation in Lung Injury: Insights From In\u00a0Vitro and In\u00a0Vivo Models"],"prefix":"10.1002","volume":"77","author":[{"given":"Aleena","family":"Varughese","sequence":"first","affiliation":[{"name":"Cell Biology and Molecular Genetics Division Yenepoya Research Center, Yenepoya (Deemed to be University)  Mangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akarsha","family":"Balnadupete","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Centre at Tyler  Tyler Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathimath Muneesa","family":"Moideen","sequence":"additional","affiliation":[{"name":"IQRAA Centre for Research and Development, IQRAA International Hospital and Research Centre  Calicut Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeena Thrikkandiyoor","family":"Madambath","sequence":"additional","affiliation":[{"name":"Cell Biology and Molecular Genetics Division Yenepoya Research Center, Yenepoya (Deemed to be University)  Mangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakshitha","family":"Charavu","sequence":"additional","affiliation":[{"name":"Cell Biology and Molecular Genetics Division Yenepoya Research Center, Yenepoya (Deemed to be University)  Mangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirana","family":"Mugaranja","sequence":"additional","affiliation":[{"name":"Cell Biology and Molecular Genetics Division Yenepoya Research Center, Yenepoya (Deemed to be University)  Mangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punya","family":"Sunil","sequence":"additional","affiliation":[{"name":"Division of Data Analytics, Bioinformatics and Structural Biology (DABS) Yenepoya Research Centre, Yenepoya (Deemed to be University)  Mangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. M.","family":"Dhivya Dharsini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Alagappa University Karaikudi  Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"ArunBharathi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Alagappa University Karaikudi  Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-3561","authenticated-orcid":false,"given":"Yashodhar P.","family":"Bhandary","sequence":"additional","affiliation":[{"name":"Cell Biology and Molecular Genetics Division Yenepoya Research Center, Yenepoya (Deemed to be University)  Mangalore India"},{"name":"Specialized Research Unit Yenepoya Medical College and Hospital, Yenepoya (Deemed to be University)  Mangalore Karnataka 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