Research ArticlePulmonary fibrosis

Caveolin-1–derived peptide limits development of pulmonary fibrosis

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Science Translational Medicine  11 Dec 2019:
Vol. 11, Issue 522, eaat2848
DOI: 10.1126/scitranslmed.aat2848

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Limiting lung disease

Fibrotic foci that form during idiopathic pulmonary fibrosis (IPF), a type of progressive and fatal interstitial lung disease, alter lung architecture, leading to cell death and loss of lung function. Marudamuthu et al. developed a caveolin-1–derived peptide, CSP7, that inhibited apoptosis of alveolar epithelial progenitor cells and activation of fibrotic lung fibroblasts. When delivered to three mouse models of lung fibrosis, CSP7 reduced extracellular matrix deposition, promoted epithelial cell survival, and improved lung function. CSP7 was also effective when administered ex vivo to lung tissue or cells isolated from people with end-stage IPF. These results support further development of CSP7 as a potential treatment.


Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with a median 5-year survival of ~20%. Current U.S. Food and Drug Administration–approved pharmacotherapies slow progression of IPF, providing hope that even more effective treatments can be developed. Alveolar epithelial progenitor type II cell (AEC) apoptosis and proliferation, and accumulation of activated myofibroblasts or fibrotic lung fibroblasts (fLfs) contribute to the progression of IPF. Full-length caveolin-1 scaffolding domain peptide (CSP; amino acids 82 to 101 of Cav1: DGIWKASFTTFTVTKYWFYR) inhibits AEC apoptosis and fLf activation and expansion and attenuates PF in bleomycin (BLM)–induced lung injury in mice. Like full-length CSP, a seven–amino acid deletion fragment of CSP, CSP7 (FTTFTVT), demonstrated antifibrotic effects in murine models of lung fibrosis. When CSP7 was administered during the fibrotic phase in three preclinical models [single-dose BLM, repeated-dose BLM, and adenovirus expressing constitutively active transforming growth factor–β1 (Ad-TGF-β1)–induced established PF], CSP7 reduced extracellular matrix (ECM) markers characteristic of PF, increased AEC survival, and improved lung function. CSP7 is amenable to both systemic (intraperitoneal) or direct lung delivery in a nebulized or dry powder form. Furthermore, CSP7 treatment of end-stage human IPF lung tissue explants attenuated ECM production and promoted AEC survival. Ames testing for mutagenicity and in vitro human peripheral blood lymphocyte and in vivo mouse micronucleus transformation assays indicated that CSP7 is not carcinogenic. Together, these findings support the further development of CSP7 as an antifibrotic treatment for patients with IPF or other interstitial lung diseases.

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