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Fingolimod, a Sphingosine-1-Phosphate Receptor Modulator Prevents Neonatal Bronchopulmonary Dysplasia and subsequent Airway Remodeling in a Murine Model.
Sudhadevi, Tara; Annadi, Akanksha; Basa, Prathima; Jafri, Anjum; Natarajan, Viswanathan; Harijith, Anantha.
Afiliación
  • Sudhadevi T; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
  • Annadi A; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
  • Basa P; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
  • Jafri A; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, United States.
  • Natarajan V; Pharmacology (MC868), University of Illinois at Chicago, Chicago, IL, United States.
  • Harijith A; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
J Appl Physiol (1985) ; 2024 Sep 12.
Article en En | MEDLINE | ID: mdl-39262336
ABSTRACT
Neonatal bronchopulmonary dysplasia (BPD) is associated with alveolar simplification and airway remodeling. Airway remodeling leads to deformation of airways characterized by peribronchial collagen deposition and hypertrophy of airway smooth muscle, which contribute to the narrowing of airways. Poorly developed lungs contribute to reduced lung function that deteriorates with the passage of time. We have earlier shown that sphingosine kinase 1 (SPHK 1)/ sphingosine-1-phosphate (S1P) /S1P receptor1 (S1PR1) signaling play a role in the pathogenesis of BPD. In this study, we investigated the role of fingolimod or FTY720, a known S1PR1 modulator approved for treatment of multiple sclerosis in the treatment of BPD. Fingolimod promotes degradation of S1PR1 by preventing its recycling thus serving as the equivalent of an inhibitor. Exposure of neonatal mice to hyperoxia enhanced the expression of S1PR1 in both airways and alveoli as compared to normoxia. This increased expression of S1PR1 in the airways persisted into adulthood accompanied by airway remodeling and airway hyperreactivity (AHR) post neonatal hyperoxia. Intranasal fingolimod at a much lower dose compared to intraperitoneal route of administration during neonatal hyperoxia improved alveolarization in neonates and reduced airway remodeling and AHR in adult mice associated with improved lung function. The intranasal route was not associated with leucopenia seen with intraperitoneal route of administration of the drug. An increase in S1PR1 expression in the airways was associated with an increase in the expression of enzyme lysyl oxidase (LOX) in the airways following hyperoxia which was suppressed by fingolimod. This association warrants further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Appl Physiol (1985) Asunto de la revista: FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Appl Physiol (1985) Asunto de la revista: FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos