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Current Opinion in Rheumatology:
doi: 10.1097/BOR.0b013e3283103d27
Raynaud phenomenon, scleroderma, overlap syndromes and other fibrosing syndromes: Edited by John Varga

Caveolin-1, transforming growth factor-β receptor internalization, and the pathogenesis of systemic sclerosis

Del Galdo, Francescoa; Lisanti, Michael Pb; Jimenez, Sergio Aa

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Abstract

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-β (TGF-β) signaling owing to its participation in TGF-β receptor internalization. TGF-β receptor internalized through caveolin-1 lipid rafts undergoes rapid degradation, effectively decreasing TGF-β 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-β 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-β 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.

© 2008 Lippincott Williams & Wilkins, Inc.

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