{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:04:09Z","timestamp":1785927849542,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Airway remodelling is a critical feature of chronic lung diseases. Epithelial\u2010mesenchymal transition (EMT) represents an important source of myofibroblasts, contributing to airway remodelling. Here, we investigated the sphingosine\u20101\u2010phosphate (S1P) role in EMT and its involvement in asthma\u2010related airway dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A549 cells were used to assess the S1P effect on EMT and its interaction with TGF\u2010\u03b2 signalling. To assess the S1P role in vivo and its impact on lung function, two experimental models of asthma were used by exposing BALB\/c mice to subcutaneous administration of either S1P or ovalbumin (OVA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Following incubation with TGF\u2010\u03b2 or S1P, A549 acquire a fibroblast\u2010like morphology associated with an increase of mesenchymal markers and down\u2010regulation of the epithelial. These effects are reversed by treatment with the TGF\u2010\u03b2 receptor antagonist LY2109761. Systemic administration of S1P to BALB\/c mice induces asthma\u2010like disease characterized by mucous cell metaplasia and increased levels of TGF\u2010\u03b2, IL\u201033 and FGF\u20102 within the lung. The bronchi harvested from S1P\u2010treated mice display bronchial hyperresponsiveness associated with overexpression of the mesenchymal and fibrosis markers and reduction of the epithelial.The S1P\u2010induced switch from the epithelial toward the mesenchymal pattern correlates to a significant increase of lung resistance and fibroblast activation. TGF\u2010\u03b2 blockade, in S1P\u2010treated mice, abrogates these effects. Finally, inhibition of sphingosine kinases by SK1\u2010II in OVA\u2010sensitized mice, abrogates EMT, pulmonary TGF\u2010\u03b2 up\u2010regulation, fibroblasts recruitment and airway hyperresponsiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Targeting S1P\/TGF\u2010\u03b2 axis may hold promise as a feasible therapeutic target to control airway dysfunction in asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15754","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T05:53:09Z","timestamp":1637905989000},"page":"1753-1768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Sphingosine\u20101\u2010phosphate\/TGF\u2010\u03b2 axis drives epithelial mesenchymal transition in asthma\u2010like disease"],"prefix":"10.1111","volume":"179","author":[{"given":"Maria A.","family":"Riemma","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Cerqua","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Irollo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Bertolino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Camerlingo","sequence":"additional","affiliation":[{"name":"RCCS INT Cellular Biology and Bioterapy\u2010 Research Department National Cancer Institute G. 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Pascale Foundation  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Terlizzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA) University of Salerno  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Spaziano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine L. 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