Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.
Cell Cycle
; 12(14): 2248-54, 2013 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-24067367
ABSTRACT
Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1(-/-)) and Cav-2-deficient mice (Cav-2(-/-)) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2(-/-) mice, but not Cav-1(-/-) mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2(-/-) mice was not associated with alterations in the TGF-ß signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2(-/-) mice. Since Cav-1(-/-) mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar
/
Regulación de la Expresión Génica
/
Caveolina 1
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Caveolina 2
/
Lesión Pulmonar Aguda
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Cycle
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos