Document Detail


Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis.
MedLine Citation:
PMID:  21498628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prior work has shown that transforming growth factor-β (TGF-β) can mediate transition of alveolar type II cells into mesenchymal cells in mice. Evidence this occurs in humans is limited to immunohistochemical studies colocalizing epithelial and mesenchymal proteins in sections of fibrotic lungs. To acquire further evidence that epithelial-to-mesenchymal transition occurs in the lungs of patients with idiopathic pulmonary fibrosis (IPF), we studied alveolar type II cells isolated from fibrotic and normal human lung. Unlike normal type II cells, type II cells isolated from the lungs of patients with IPF express higher levels of mRNA for the mesenchymal proteins type I collagen, α-smooth muscle actin (α-SMA), and calponin. When cultured on Matrigel/collagen, human alveolar type II cells maintain a cellular morphology consistent with epithelial cells and expression of surfactant protein C (SPC) and E-cadherin. In contrast, when cultured on fibronectin, the human type II cells flatten, spread, lose expression of pro- SPC, and increase expression of vimentin, N-cadherin, and α-SMA; markers of mesenchymal cells. Addition of a TGF-β receptor kinase inhibitor (SB431542) to cells cultured on fibronectin inhibited vimentin expression and maintained pro-SPC expression, indicating persistence of an epithelial phenotype. These data suggest that alveolar type II cells can acquire features of mesenchymal cells in IPF lungs and that TGF-β can mediate this process.
Authors:
Cecilia Marmai; Rachel E Sutherland; Kevin K Kim; Gregory M Dolganov; Xiaohui Fang; Sophia S Kim; Shuwei Jiang; Jeffery A Golden; Charles W Hoopes; Michael A Matthay; Harold A Chapman; Paul J Wolters
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-15
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  301     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-04     Completed Date:  2011-08-31     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L71-8     Citation Subset:  IM    
Affiliation:
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143-0111, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Separation
Epithelial-Mesenchymal Transition / drug effects
Fibronectins / pharmacology
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation* / drug effects
Humans
Idiopathic Pulmonary Fibrosis / genetics*,  pathology
Immunohistochemistry
Lasers
Mesoderm / drug effects,  metabolism*
Mice
Microdissection
Pneumocytes / drug effects,  metabolism*
Proteins / genetics*,  metabolism
Reproducibility of Results
Transforming Growth Factor beta / pharmacology
Grant Support
ID/Acronym/Agency:
HL085290/HL/NHLBI NIH HHS; HL104422/HL/NHLBI NIH HHS; HL44712/HL/NHLBI NIH HHS; R01 HL044712/HL/NHLBI NIH HHS; R01 HL044712-21/HL/NHLBI NIH HHS; R01 HL051854/HL/NHLBI NIH HHS; R01 HL051854-18/HL/NHLBI NIH HHS; R01 HL051854-19/HL/NHLBI NIH HHS; R21 HL104422/HL/NHLBI NIH HHS; R21 HL104422-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Proteins; 0/Transforming Growth Factor beta
Comments/Corrections

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