Document Detail

Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells.
MedLine Citation:
PMID:  17570215     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Barrett's esophagus (BE) is a metaplastic condition in which normal squamous esophageal epithelium is replaced by columnar epithelium. It is proposed that one of the possible mechanisms is dedifferentiation of squamous epithelium into columnar epithelium. The pathophysiology through which this metaplasia occurs is unknown. A recent study by serial analysis of gene expression showed that bone morphogenetic protein 4 (BMP-4) is uniquely expressed in BE. In this study, the role of the BMP pathway in the metaplastic transformation of normal squamous cells into columnar cells was examined. METHODS: Tissues from patients with esophagitis and BE and in an esophagitis-BE rat model were examined for the activation of the BMP pathway. Short-term cultures of primary normal squamous esophageal cells were treated with BMP-4, and cell biological changes were examined by Western blot analysis, immunohistochemistry, and microarrays. RESULTS: In both human and rat tissues, the BMP pathway proved to be activated in esophagitis and BE. Upon incubation of squamous cell cultures with BMP-4, the cytokeratin expression pattern showed a shift that was consistent with columnar epithelium. Involvement of the BMP pathway was suggested by up-regulation of Phosphorylated-Smad 1/5/8 (P-Smad 1/5/8) that was effectively blocked by Noggin, a BMP antagonist. Comparison of the gene expression profiles of squamous cells, BMP-4-treated squamous cells, and BE cells showed a significant shift in the profile of the BMP-4-treated squamous cells toward that of the cultured BE cells. CONCLUSIONS: These results suggest that the BMP pathway could play a role in the transformation of normal esophageal squamous cells into columnar cells.
Francesca Milano; Jantine W P M van Baal; Navtej S Buttar; Agnieszka M Rygiel; Floor de Kort; Cathrine J DeMars; Wilda D Rosmolen; Jacques J G H M Bergman; Jan VAn Marle; Kenneth K Wang; Maikel P Peppelenbosch; Kausilia K Krishnadath
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-19
Journal Detail:
Title:  Gastroenterology     Volume:  132     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-15     Completed Date:  2007-07-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2412-21     Citation Subset:  AIM; IM    
Laboratory of Experimental Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
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MeSH Terms
Aged, 80 and over
Barrett Esophagus / metabolism*,  pathology*
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins / metabolism*,  pharmacology
Cells, Cultured
Esophagitis / metabolism*,  pathology*
Esophagus / cytology,  drug effects,  metabolism*,  pathology*
Genome, Human
Keratins / metabolism
Microarray Analysis
Middle Aged
Rats, Sprague-Dawley
Reg. No./Substance:
0/BMP4 protein, human; 0/Bmp4 protein, rat; 0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 68238-35-7/Keratins

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