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Cited by 397Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisCaveolin-1 and cellular processesPulmonary Hypertension Research and Treatments

Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis

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Wang, Xiao Mei, Zhang, Yingze, Kim, Hong Pyo, Zhou, Zhihong, Feghali-Bostwick, Carol A., Liu, Fang, Ifedigbo, Emeka, Xu, Xiaohui +3 more·2006·The Journal of Experimental Medicine
DOI 10.1084/jem.20061536PMC PMC1850940
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder characterized by activation of fibroblasts and overproduction of extracellular matrix (ECM). Caveolin-1 (cav-1), a principal component of caveolae, has been implicated in the regulation of numerous signaling pathways and biological processes. We observed marked reduction of cav-1 expression in lung tissues and in primary pulmonary fibroblasts from IPF patients compared with controls. We also demonstrated that cav-1 markedly ameliorated bleomycin (BLM)-induced pulmonary fibrosis, as indicated by histological analysis, hydroxyproline content, and immunoblot analysis. Additionally, transforming growth factor beta1 (TGF-beta1), the well-known profibrotic cytokine, decreased cav-1 expression in human pulmonary fibroblasts. cav-1 was able to suppress TGF-beta1-induced ECM production in cultured fibroblasts through the regulation of the c-Jun N-terminal kinase (JNK) pathway. Interestingly, highly activated JNK was detected in IPF- and BLM-instilled lung tissue samples, which was dramatically suppressed by ad-cav-1 infection. Moreover, JNK1-null fibroblasts showed reduced smad signaling cascades, mimicking the effects of cav-1. This study indicates a pivotal role for cav-1 in ECM regulation and suggests a novel therapeutic target for patients with pulmonary fibrosis.

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  • Augmentation of endogenous Cav-1 levels and supplementation of exogenous caveolin scaffolding domain peptide have been shown to suppress lung fibrosis.

    “Augmentation of endogenous Cav-1 levels and supplementation of exogenous caveolin scaffolding domain (CSD) peptide have been shown to suppress lung fibrosis7,10,11,13,14.”

    From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [7]

    The Discussion (page not specified) reports that adenoviral overexpression of Cav-1 reduced fibrosis in a bleomycin-treated mouse model. The Results also report reduced TGF-β1-induced matrix production after Cav-1 overexpression. Our copy does not report supplementation with a caveolin scaffolding domain peptide, so that part of the claim is not supported by this source. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Caveolin-1 protein is a structural protein that plays a critical role in regulating lung repair and cellular movement by restoring pathways that both promote epithelial health and halt fibrosis in the lung.

    “Caveolin-1 protein (Cav-1) is a structural protein that plays a critical role in regulating lung repair and cellular movement by restoring pathways that both promote epithelial health and halt fibrosis in the lung7–9.”

    From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [7]

    The introductory passage describes cav-1 as a scaffolding protein, and the Results report that increasing cav-1 suppresses TGF-β1–induced extracellular-matrix production in pulmonary fibroblasts. The paper supports an antifibrotic role, but the cited passages do not establish that cav-1 regulates cellular movement or restores pathways promoting epithelial health and lung repair. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Research works printed but not linked: 44

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Cited by

Sorted by citations

Authors
Wang, X. M., Zhang, Y., Kim, H. P., Zhou, Z., Feghali-Bostwick, C. A., Liu, F., Ifedigbo, E., Xu, X., Oury, T. D., Kaminski, N., & Choi, A. M. K.
Affiliations
  • University of Pittsburgh (US)
  • 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2006-12-18
Volume
203
Issue
13
Pages
2895-2906
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20061536
PMC
PMC1850940
OpenAlex
W2112871329
Cited by
397
References
0
Citations by year
2026: 9 · 2025: 12 · 2024: 16 · 2023: 12 · 2022: 12 · 2021: 19 · 2020: 24 · 2019: 16 · 2018: 21 · 2017: 29 · 2016: 23 · 2015: 18 · 2014: 27 · 2013: 27 · 2012: 29
FWCI
17.08
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01-HL073745-01, R01HL055330, R01HL063700, P01-HL70807, R01HL55330, R01HL079904, R01HL060234, P01HL070807, R01HL073745)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords
caveolin-1, idiopathic pulmonary fibrosis, pulmonary fibrosis, lung fibroblasts, extracellular matrix synthesis, TGF-β1, JNK signaling, Smad signaling, bleomycin-induced fibrosis, caveolae, therapeutic target
MeSH terms
Actins, Animals, Bleomycin, Epithelial Cells, Extracellular Matrix, Fibroblasts, Fibronectins, Fibrosis, Humans, Hydroxyproline, Lung, Mice, Inbred C57BL, Phosphorylation, Pulmonary Fibrosis, Transfection, Gene Expression, Mice, Knockout, Collagen Type I, RNA, Small Interfering, JNK Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 8, Caveolin 1, Mice, Smad2 Protein, Transforming Growth Factor beta1

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