Caveolin-1, TGF-β receptor internalization, and the pathogenesis of systemic sclerosis

Authors

Francesco Del Galdo, Jefferson Institute of Molecular Medicine, Department of Dermatology and Cutaneous Biology, Thomas Jefferson UniversityFollow
Michael P. Lisanti, Kimmel Cancer Center, Departments of Cancer Biology, Medical Oncology, and Biochemistry, Stem Cell Biology and Regenerative Medicine Center, Thomas Jefferson UniversityFollow
Sergio A. Jimenez, Jefferson Institute of Molecular Medicine, Department of Dermatology and Cutaneous Biology, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

11-2008

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Current Opinion in Rheumatology. 2008, 20(6): 713–719. The published version is available at DOI: 10.1097/BOR.0b013e3283103d27. Copyright © Lippincott Williams & Wilkins

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-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.

Recommended Citation

Del Galdo, Francesco; Lisanti, Michael P.; and Jimenez, Sergio A., "Caveolin-1, TGF-β receptor internalization, and the pathogenesis of systemic sclerosis" (2008). Jefferson Institute of Molecular Medicine Papers and Presentations. Paper 4.
https://jdc.jefferson.edu/jimmfp/4