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Journal article
Sphingosine-1-phosphate/TGF-β axis drives epithelial mesenchymal transition in asthma-like disease
British journal of pharmacology, v 179(8), pp 1753-1768
Apr 2022
PMID: 34825370
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Airway remodelling is a critical feature of chronic lung diseases. Epithelial-mesenchymal transition (EMT) represents an important source of myofibroblasts, contributing to airway remodelling. Here, we investigated the sphingosine-1-phosphate (S1P) role in EMT and its involvement in asthma-related airway dysfunction.
A549 cells were used to assess the S1P effect on EMT and its interaction with TGF-β 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).
Following incubation with TGF-β or S1P, A549 acquire a fibroblast-like morphology associated with an increase of mesenchymal markers and down-regulation of the epithelial. These effects are reversed by treatment with the TGF-β receptor antagonist LY2109761. Systemic administration of S1P to BALB/c mice induces asthma-like disease characterized by mucous cell metaplasia and increased levels of TGF-β, IL-33 and FGF-2 within the lung. The bronchi harvested from S1P-treated mice display bronchial hyperresponsiveness associated with overexpression of the mesenchymal and fibrosis markers and reduction of the epithelial.The S1P-induced switch from the epithelial toward the mesenchymal pattern correlates to a significant increase of lung resistance and fibroblast activation. TGF-β blockade, in S1P-treated mice, abrogates these effects. Finally, inhibition of sphingosine kinases by SK1-II in OVA-sensitized mice, abrogates EMT, pulmonary TGF-β up-regulation, fibroblasts recruitment and airway hyperresponsiveness.
Targeting S1P/TGF-β axis may hold promise as a feasible therapeutic target to control airway dysfunction in asthma.
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Details
- Title
- Sphingosine-1-phosphate/TGF-β axis drives epithelial mesenchymal transition in asthma-like disease
- Creators
- Maria A Riemma - University of Naples Federico IIIda Cerqua - University of Naples Federico IIBarbara Romano - University of Naples Federico IIElena Irollo - Drexel UniversityAntonio Bertolino - University of Naples Federico IIRosa Camerlingo - National Cancer Institute G. Pascale Foundation, RCCS INT Cellular Biology and Bioterapy- Research Department, Naples, Italy.Elisabetta Granato - University of Naples Federico IIGiuseppina Rea - Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"Stefania Scala - Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"Michela Terlizzi - University of SalernoGiuseppe Spaziano - University of Campania "Luigi Vanvitelli"Rosalinda Sorrentino - University of SalernoBruno D'Agostino - University of Campania "Luigi Vanvitelli"Fiorentina Roviezzo - University of Naples Federico IIGiuseppe Cirino - University of Naples Federico II
- Publication Details
- British journal of pharmacology, v 179(8), pp 1753-1768
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000744951900001
- Scopus ID
- 2-s2.0-85123176035
- Other Identifier
- 991019168216904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy