Document Detail

Differential susceptibility to epithelial-mesenchymal transition (EMT) of alveolar, bronchial and intestinal epithelial cells in vitro and the effect of angiotensin II receptor inhibition.
MedLine Citation:
PMID:  20848133     Owner:  NLM     Status:  MEDLINE    
The generation of myofibroblasts via epithelial-mesenchymal transition (EMT), a process through which epithelial cells lose their polarity and become motile mesenchymal cells, is a proposed contributory factor in fibrosis of a number of organs. Currently, it remains unclear to what extent epithelia of the upper airways and large intestine are susceptible to this process. Herein, we investigated the ability of model cell lines of alveolar (A549), bronchial (Calu-3) and colonic (Caco-2) epithelial cells to undergo EMT when challenged with transforming growth factor-β1 (TGF-β1) and other pro-inflammatory cytokines. Western blot and immunofluorescence microscopy demonstrated that A549 cells readily underwent EMT, as evidenced by a spindle-like morphology, increase in the mesenchymal marker, vimentin, and down-regulation of E-cadherin, an epithelial marker. In contrast, neither Calu-3 nor Caco-2 cells exhibited morphological changes nor alterations in marker expression associated with EMT. Moreover, whilst stimulation of A549 cells enhanced migration and reduced their proliferative capacity, no such effect was observed in epithelial cell lines of the bronchus or colon. In addition, concomitant treatment of A549 cells with telmisartan, an angiotensin II receptor antagonist with antifibrotic properties, was found to reduce cytokine-induced collagen I production and cell migration, although expression levels of vimentin and E-cadherin remained unaltered. Mechanistically, telmisartan failed to inhibit phosphorylation of Smad2/3. Together, these results, using representative in vitro models of the alveolus, bronchus and colon, tentatively suggest that epithelial cell plasticity and susceptibility to EMT may differ depending on its tissue origin. Furthermore, our investigations point to the beneficial effect of telmisartan in partial abrogation of alveolar EMT.
Stephen T Buckley; Carlos Medina; Carsten Ehrhardt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-17
Journal Detail:
Title:  Cell and tissue research     Volume:  342     ISSN:  1432-0878     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-01-19     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  39-51     Citation Subset:  IM    
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers / pharmacology
Antigens, Differentiation / biosynthesis
Benzimidazoles / pharmacology
Benzoates / pharmacology
Bronchi / metabolism*,  pathology
Caco-2 Cells
Cell Movement / drug effects
Collagen Type I / biosynthesis
Epithelial Cells / metabolism*,  pathology
Epithelial-Mesenchymal Transition*
Intestines / metabolism*,  pathology
Phosphorylation / drug effects
Pulmonary Alveoli / metabolism*,  pathology
Receptors, Angiotensin / metabolism*
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Transforming Growth Factor beta1 / pharmacology*
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Antigens, Differentiation; 0/Benzimidazoles; 0/Benzoates; 0/Collagen Type I; 0/Receptors, Angiotensin; 0/SMAD2 protein, human; 0/SMAD3 protein, human; 0/Smad2 Protein; 0/Smad3 Protein; 0/Transforming Growth Factor beta1; U5SYW473RQ/telmisartan

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