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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/L1007    most recent 90207.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Le Saux, O. Articles by Jourdan-Le Saux, C. Search for Related Content PubMed PubMed Citation Articles by Le Saux, O. Articles by Jourdan-Le Saux, C.

The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties

¹Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii; ²Department of Anatomy and Cell Biology, McGill University, Montréal, Québec, Canada; ³Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas; ⁴Department of Biochemistry, University of Texas Health Center, Tyler, Texas; and ⁵Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii

Submitted 22 February 2008 ; accepted in final form 4 October 2008

Caveolin-1 (cav1) is a 22-kDa membrane protein essential to the formation of small invaginations in the plasma membrane, called caveolae. The cav1 gene is expressed primarily in adherent cells such as endothelial and smooth muscle cells and fibroblasts. Caveolae contain a variety of signaling receptors, and cav1 notably downregulates transforming growth factor (TGF)-β signal transduction. In pulmonary pathologies such as interstitial fibrosis or emphysema, altered mechanical properties of the lungs are often associated with abnormal ECM deposition. In this study, we examined the physiological functions and the deposition of ECM in cav1^–/– mice at various ages (1–12 mo). Cav1^–/– mice lack caveolae and by 3 mo of age have significant reduced lung compliance and increased elastance and airway resistance. Pulmonary extravasation of fluid, as part of the cav1^–/– mouse phenotype, probably contributed to the alteration of compliance, which was compounded by a progressive increase in deposition of collagen fibrils in airways and parenchyma. We also found that the increased elastance was caused by abundant elastic fiber deposition primarily around airways in cav1^–/– mice at least 3 mo old. These observed changes in the ECM composition probably also contribute to the increased airway resistance. The higher deposition of collagen and elastic fibers was associated with increased tropoelastin and col12 and col31 gene expression in lung tissues, which correlated tightly with increased TGF-β/Smad signal transduction. Our study illustrates that perturbation of cav1 function may contribute to several pulmonary pathologies as the result of the important role played by cav1, as part of the TGF-β signaling pathway, in the regulation of the pulmonary ECM.

transforming growth factor-β; extracellular matrix; lung physiology