Document Detail

Caveolin-1, transforming growth factor-beta receptor internalization, and the pathogenesis of systemic sclerosis.
MedLine Citation:
PMID:  18949888     Owner:  NLM     Status:  MEDLINE    
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.
Francesco Del Galdo; Michael P Lisanti; Sergio A Jimenez
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Publication Detail:
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:
Title:  Current opinion in rheumatology     Volume:  20     ISSN:  1531-6963     ISO Abbreviation:  Curr Opin Rheumatol     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-24     Completed Date:  2009-01-15     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9000851     Medline TA:  Curr Opin Rheumatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  713-9     Citation Subset:  IM    
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MeSH Terms
Caveolae / metabolism
Caveolin 1 / deficiency,  genetics,  metabolism*
Mice, Knockout
Models, Biological
Pulmonary Fibrosis / etiology,  metabolism
Receptors, Transforming Growth Factor beta / metabolism*
Scleroderma, Systemic / complications,  etiology*,  metabolism,  therapy
Signal Transduction
Grant Support
R01 AR019616/AR/NIAMS NIH HHS; R01 AR019616-30/AR/NIAMS NIH HHS; R01 AR019616-31/AR/NIAMS NIH HHS; R01 AR019616-32/AR/NIAMS NIH HHS; R01 AR055660/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
Reg. No./Substance:
0/CAV1 protein, human; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Receptors, Transforming Growth Factor beta

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