Novel findings in the pathogenesis of esophageal columnar metaplasia or Barrett's esophagus.
OBJECTIVE
In esophageal metaplasia the transdifferentiation of the epithelium is the result of longstanding gastroesophageal reflux disease that causes inflammation of the esophageal squamous mucosa, and occasionally is followed by replacement of the squamous epithelium by a columnar type of mucosa. For a long time, the molecular mechanisms involved in metaplasia were poorly understood. This review focuses on several recent findings on the molecular mechanisms involved in esophageal columnar metaplasia.


RESULTS
Our recent findings on bone morphogenetic protein 4 and other recent discoveries in the field of cell signaling that take place during the sequence of inflammation and epithelial transdifferentiation are highlighted. In this process, several embryonic pathways that were silenced in the adult esophagus, and factors that are normally involved in the homeostasis of the large intestine, seem to be induced. These factors may mediate transdifferentiation of the esophageal epithelium.


CONCLUSIONS
Although there are many aspects that need further investigation, it seems that in columnar metaplasia of the esophagus inductive morphogenes such as bone morphogenetic protein 4 are important for development and differentiation. Development of specialized intestinal type of metaplasia is the result of a succession of events, in which the effect of stromal factors is followed by expression of intestine-specific factors.
Krishnadath
Kausilia K
KK
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. k.k.krishnadath@amc.uva.nl
D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D004947:Esophagus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008679:Metaplasia; D009092:Mucous Membrane / Q000378:metabolism; D015854:Up-Regulation
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins