Journal
CURRENT OPINION IN RHEUMATOLOGY
Volume 20, Issue 6, Pages 713-719Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/BOR.0b013e3283103d27
Keywords
caveolin-1; collagen; fibrosis; idiopathic pulmonary fibrosis; systemic sclerosis; transforming growth factor-beta
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Funding
- NIH/NIAMS [R01-AR-019616]
- John Murray Foundation
- NIH/NCI [R01-CA-80250, R01-CA-098779, R01-CA-120876]
- American Association for Cancer Research (AACR)
- Department of Defense-Breast Cancer Research Program
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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 internal zed 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 fibros is 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 pathogeneis 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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