The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online December 18, 2006
doi:10.1084/jem.20061536
The Journal of Experimental Medicine, Vol. 203, No. 13, 2895-2906
The Rockefeller University Press, 0022-1007 $30.00
© 2006 Wang et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 5501K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, X. M.
Right arrow Articles by Choi, A. M.K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, X. M.
Right arrow Articles by Choi, A. M.K.
Right arrowPubmed/NCBI databases
*Gene*GEO DataSet
*GEO Profiles*HomoloGene
*OMIM*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*BLEOMYCIN
Medline Plus Health Information
*Pulmonary Fibrosis
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

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

Xiao Mei Wang1, Yingze Zhang1, Hong Pyo Kim1, Zhihong Zhou1, Carol A. Feghali-Bostwick1, Fang Liu1, Emeka Ifedigbo1, Xiaohui Xu2, Tim D. Oury3, Naftali Kaminski1, and Augustine M.K. Choi1

1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213
2 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261
3 Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261

CORRESPONDENCE Augustine M.K. Choi: choiam{at}upmc.edu

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 ß1 (TGF-ß1), the well-known profibrotic cytokine, decreased cav-1 expression in human pulmonary fibroblasts. cav-1 was able to suppress TGF-ß1–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.

Abbreviations used: {alpha}-SMA, {alpha}–smooth muscle actin; BLM, bleomycin; cav-1, caveolin-1; ECM, extracellular matrix; ERK, extracellular signal–regulated protein kinase; H&E, hematoxylin and eosin; IPF, idiopathic pulmonary fibrosis; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS