{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:33:45Z","timestamp":1770777225687,"version":"3.50.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LYMPHOGENiX Ltd.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n Pulmonary fibrosis remains a major clinical challenge with limited treatment options. Recent studies have suggested that fibroblasts, when stimulated by specific cytokines, may acquire lymphangiogenic and antifibrotic properties contributing to tissue repair.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Human and rat pulmonary fibroblasts (PFs) were stimulated with TNF-\u03b1 and IL-4 to induce lymphangiogenic and antifibrotic characteristics. In vitro analyses assessed gene expression, cytokine secretion, tube formation capacity, and immunogenicity. Therapeutic efficacy was evaluated in a rat model of bleomycin-induced pulmonary fibrosis following allogeneic PF transplantation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cytokine-stimulated PFs exhibited upregulation of\n ADM<\/jats:italic>\n and\n VEGFC<\/jats:italic>\n , enhanced tube formation capacity, and minimal expression of immunogenic markers. In vivo, allogeneic PF transplantation significantly reduced fibrotic lesion and plasma SP-D levels compared to controls. Gene expression analyses demonstrated downregulation of fibrosis-associated markers after treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Cytokine-stimulated pulmonary fibroblasts may serve as a novel cell source for antifibrotic therapy by modulating lymphangiogenesis and tissue remodeling, providing a potential alternative to conventional stem cell-based approaches for fibrotic lung diseases.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0342528","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:30:11Z","timestamp":1770748211000},"page":"e0342528","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary fibroblasts activated by the addition of TNF-\u03b1 and IL-4 enhance lymphangiogenic capacity and ameliorate lung fibrosis in an allogeneic rat 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