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

Mei Wang Xiao, Yingze Zhang, Pyo Kim Hong, Zhihong Zhou, Carol A. Feghali-Bostwick, Fang Liu, Emeka Ifedigbo, Xiaohui Xu, Tim D. Oury, Naftali Kaminski, Augustine M.K. Choi

Research output: Contribution to journalArticle

290 Scopus citations

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 β1 (TGF-β1), the well-known profibrotic cytokine, decreased cav-1 expression in human pulmonary fibroblasts. cav-1 was able to suppress TGF-β1-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. JEM

Original languageEnglish (US)
Pages (from-to)2895-2906
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number13
DOIs
StatePublished - Dec 25 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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