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New insights into the factors that cause Barrett's oesophagus
The mechanisms responsible for the transformation of the normal oesophageal squamous epithelium into the metaplastic intestinal epithelium that characterises Barrett's oesophagus are poorly understood, but are essential to know in order to develop better ways for preventing Barrett's oesophagus. Prior work by the authors of this study and by others has shown that a transcription factor called CDX2 is one of the mechanisms involved in the formation of Barrett's oesophagus. Kazumori and colleagues now show that Kruppel-Like Factor 4 (KLF4), a key protein that regulates the differentiation of the epithelium of the gastrointestinal tract, is a second transcription factor strongly expressed in Barrett's epithelium that is induced by bile acids. Importantly, they have shown that KLF4 and CDX2 cooperate to induce each other's expression and that KLF4 induces the expression of the mucin protein MUC2, which is involved in intestinal metaplasia. Moreover, they also show that the inflammation related signalling pathway, NF-κB, is also involved in this process. This study advances our understanding of the transcriptional network related to KLF4 and CDX2 that affects the development of Barrett's oesophagus. KLF4 and CDX2 are possible molecular targets for the prevention of Barrett's oesophagus, and therapies directed at these proteins may yield a …
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