| Caveolin-1, transforming growth factor-beta receptor internalization, and the pathogenesis of systemic sclerosis. | |
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MedLine Citation:
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PMID: 18949888 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE OF REVIEW: To review the scientific literature supporting the participation of caveolin-1 in the pathogenesis of tissue fibrosis and the notion that modulation of the caveolin-1 pathway may represent a novel treatment for systemic sclerosis and other fibrotic diseases. RECENT FINDINGS: Caveolin-1 plays an important role in the regulation of transforming growth factor-beta (TGF-beta) signaling owing to its participation in TGF-beta receptor internalization. TGF-beta receptor internalized through caveolin-1 lipid rafts undergoes rapid degradation, effectively decreasing TGF-beta signaling. Studies have shown that caveolin-1 knockdown in vitro markedly increased collagen gene expression in normal human lung fibroblasts. Caveolin-1 was reduced in affected systemic sclerosis lungs and skin and in idiopathic pulmonary fibrosis lung tissues and fibroblasts. Increasing caveolin-1 expression markedly improved bleomycin-induced pulmonary fibrosis. Restoration of caveolin bioavailability employing penetratin, a cell-permeable peptide carrier for a bioactive caveolin-1 fragment, abrogated TGF-beta activation of cultured human dermal fibroblasts. Systemic administration of penetratin-caveolin-1 peptide to mice with bleomycin-induced lung fibrosis reduced fibrosis. SUMMARY: Caveolin-1 plays an important role in the regulation of TGF-beta signaling and participates in the pathogenesis of systemic sclerosis and idiopathic pulmonary fibrosis. Restoration of caveolin function employing active caveolin-1 fragments coupled to cell-permeable carrier peptides may represent a novel approach for their treatment. |
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Authors:
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Francesco Del Galdo; Michael P Lisanti; Sergio A Jimenez |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review |
Journal Detail:
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Title: Current opinion in rheumatology Volume: 20 ISSN: 1531-6963 ISO Abbreviation: Curr Opin Rheumatol Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-10-24 Completed Date: 2009-01-15 Revised Date: 2011-03-31 |
Medline Journal Info:
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Nlm Unique ID: 9000851 Medline TA: Curr Opin Rheumatol Country: United States |
Other Details:
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Languages: eng Pagination: 713-9 Citation Subset: IM |
Affiliation:
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Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107-5541, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Caveolae / metabolism Caveolin 1 / deficiency, genetics, metabolism* Humans Mice Mice, Knockout Models, Biological Pulmonary Fibrosis / etiology, metabolism Receptors, Transforming Growth Factor beta / metabolism* Scleroderma, Systemic / complications, etiology*, metabolism, therapy Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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R01 AR019616-30/AR/NIAMS NIH HHS; R01 AR019616-31/AR/NIAMS NIH HHS; R01 AR019616-32/AR/NIAMS NIH HHS; R01 AR055660-02/AR/NIAMS NIH HHS; R01 AR055660-03/AR/NIAMS NIH HHS; R01-AR-019616/AR/NIAMS NIH HHS; R01-CA-098779/CA/NCI NIH HHS; R01-CA-120876/CA/NCI NIH HHS; R01-CA-80250/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CAV1 protein, human; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Receptors, Transforming Growth Factor beta |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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