Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.
AffiliationDepartment of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA USA
MetadataShow full item record
AbstractCaveolar 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-β 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.
CitationGenetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury. 2013, 12 (14):2248-54 Cell Cycle
- Caveolin-1 deficiency protects from pulmonary fibrosis by modulating epithelial cell senescence in mice.
- Authors: Shivshankar P, Brampton C, Miyasato S, Kasper M, Thannickal VJ, Le Saux CJ
- Issue date: 2012 Jul
- Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis.
- Authors: Wang XM, Zhang Y, Kim HP, Zhou Z, Feghali-Bostwick CA, Liu F, Ifedigbo E, Xu X, Oury TD, Kaminski N, Choi AM
- Issue date: 2006 Dec 25
- Nintedanib reduces ventilation-augmented bleomycin-induced epithelial-mesenchymal transition and lung fibrosis through suppression of the Src pathway.
- Authors: Li LF, Kao KC, Liu YY, Lin CW, Chen NH, Lee CS, Wang CW, Yang CT
- Issue date: 2017 Nov
- Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system.
- Authors: Bhandary YP, Shetty SK, Marudamuthu AS, Gyetko MR, Idell S, Gharaee-Kermani M, Shetty RS, Starcher BC, Shetty S
- Issue date: 2012 Mar 1
- Caveolin-2-deficient mice show increased sensitivity to endotoxemia.
- Authors: de Almeida CJ, Witkiewicz AK, Jasmin JF, Tanowitz HB, Sotgia F, Frank PG, Lisanti MP
- Issue date: 2011 Jul 1