Article ; Online: Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling.
Matrix biology : journal of the International Society for Matrix Biology
2011 Volume 30, Issue 5-6, Page(s) 318–329
Abstract: The cardiac response to myocardial injury includes fibrotic and hypertrophic processes and a key mediator in this response is transforming growth factor-β1 (TGF-β1). Caveolin-1 (cav1), the main structural protein of caveolae, is an inhibitor of the TGF- ... ...
| Abstract | The cardiac response to myocardial injury includes fibrotic and hypertrophic processes and a key mediator in this response is transforming growth factor-β1 (TGF-β1). Caveolin-1 (cav1), the main structural protein of caveolae, is an inhibitor of the TGF-β1 signaling pathway. To examine the role of cav1 in cardiac repair, cav1 deficient (Cav1(-/-)) and wild type (WT) mice were subjected to cryoinjury of the left ventricle (LV). At baseline the two groups exhibited no inflammation, similar collagen content, and similar cardiac function. After injury, Cav1(-/-) animals displayed enhanced TGF-β1 signaling, as reflected by a 3-fold increase in the activation of the Smad2-dependent pathway and more widespread collagen deposition in the heart. Qualitative and quantitative analyses indicated that collagen deposition peaked in the WT LV 14days after injury, accompanied by increased mRNA abundance for procol1a2 (2-fold) and procol3a1 (3-fold). Collagen deposition was further enhanced in Cav1(-/-) mice, which was accompanied by reduced expression of matrix metalloproteinases MMP-8 (3-fold) and -13 mRNA (2-fold). The levels of expression of inflammatory markers of acute phase were similar between the strains However, macrophage clearance in the damaged region was delayed in Cav1(-/-) mice. We observed a 4-fold decrease in collagen deposition in Cav1(-/-) mice injected with a cav1 scaffolding domain peptide (CSD) and a 2-fold decrease in WT mice treated with the CSD. We conclude that cav1 has a direct role in reducing TGF-β1 signaling and as such might be an appropriate target for therapies to influence cardiac remodeling. |
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| MeSH term(s) | Animals ; Biomarkers ; Body Weight ; Caveolin 1/genetics ; Caveolin 1/metabolism ; Collagen/metabolism ; Cryosurgery ; Fibroblasts/metabolism ; Fibrosis/immunology ; Fibrosis/metabolism ; Gene Expression Regulation ; Heart Ventricles/metabolism ; Heart Ventricles/surgery ; Immunohistochemistry ; Macrophages/immunology ; Macrophages/metabolism ; Male ; Matrix Metalloproteinase 13/metabolism ; Matrix Metalloproteinase 8/metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Messenger/metabolism ; Signal Transduction ; Smad2 Protein/metabolism ; Transforming Growth Factor beta1/metabolism |
| Chemical Substances | Biomarkers ; Caveolin 1 ; RNA, Messenger ; Smad2 Protein ; Smad2 protein, mouse ; Transforming Growth Factor beta1 ; Collagen (9007-34-5) ; Matrix Metalloproteinase 13 (EC 3.4.24.-) ; Mmp13 protein, mouse (EC 3.4.24.-) ; Matrix Metalloproteinase 8 (EC 3.4.24.34) |
| Language | English |
| Publishing date | 2011-05-27 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1183793-7 |
| ISSN | 1569-1802 ; 0945-053X |
| ISSN (online) | 1569-1802 |
| ISSN | 0945-053X |
| DOI | 10.1016/j.matbio.2011.05.003 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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