RGD Reference Report - Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells. - Rat Genome Database

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Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells.

Authors: Milano, F  Van Baal, JW  Buttar, NS  Rygiel, AM  De Kort, F  DeMars, CJ  Rosmolen, WD  Bergman, JJ  VAn Marle, J  Wang, KK  Peppelenbosch, MP  Krishnadath, KK 
Citation: Milano F, etal., Gastroenterology. 2007 Jun;132(7):2412-21. Epub 2007 Mar 19.
RGD ID: 8699511
Pubmed: PMID:17570215   (View Abstract at PubMed)
DOI: DOI:10.1053/j.gastro.2007.03.026   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP4HumanBarrett's esophagus  IEP protein:increased expression:esophagus:RGD 
BMP4HumanBarrett's esophagus  ISOBmp4 (Rattus norvegicus)protein:increased expression:esophagus:RGD 
Bmp4RatBarrett's esophagus  ISOBMP4 (Homo sapiens)protein:increased expression:esophagus:RGD 
Bmp4RatBarrett's esophagus  IEP protein:increased expression:esophagus:RGD 
Bmp4MouseBarrett's esophagus  ISOBmp4 (Rattus norvegicus)protein:increased expression:esophagus:RGD 
Bmp4MouseBarrett's esophagus  ISOBMP4 (Homo sapiens)protein:increased expression:esophagus:RGD 
BMP4Humanesophagitis  IEP protein:increased expression:esophagus:RGD 
Bmp4Ratesophagitis  ISOBMP4 (Homo sapiens)protein:increased expression:esophagus:RGD 
Bmp4Mouseesophagitis  ISOBMP4 (Homo sapiens)protein:increased expression:esophagus:RGD 
BMP4Humanpeptic esophagitis  ISOBmp4 (Rattus norvegicus)protein:increased expression:esophagus:RGD 
Bmp4Ratpeptic esophagitis  IEP protein:increased expression:esophagus:RGD 
Bmp4Mousepeptic esophagitis  ISOBmp4 (Rattus norvegicus)protein:increased expression:esophagus:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp4  (bone morphogenetic protein 4)

Genes (Mus musculus)
Bmp4  (bone morphogenetic protein 4)

Genes (Homo sapiens)
BMP4  (bone morphogenetic protein 4)


Additional Information