Acid and bile salt up-regulate BMP4 expression in human esophageal epithelium cells.
OBJECTIVE
Barrett's esophagus (BE) with an intestinal-type epithelium is thought to be a precancerous lesion of adenocarcinoma of the esophagus. The pathophysiology of Barrett's metaplasia is poorly understood. Previous studies suggest that differentiation of multipotent cells to columnar epithelium may be one of the possible mechanisms. Bone morphogenetic protein 4 (BMP4), a factor determining the fate of cells, is up-regulated in BE and esophagitis mucosa when compared with normal squamous or non-goblet cell-containing cardiac epithelium. The aim of this study was to demonstrate that BMP4 is a molecular mediator that links etiological agents of BE to the phenotypic changes in human esophagus epithelium cells (HEECs).


METHODS
Primary cultured HEECs were used to investigate the effect of acid and bile salt on BMP4 expression and to examine the biological effects of BMP4 on HEECs.


RESULTS
Acid and bile salt increased the expression of BMP4. In addition, recombinant human BMP4 induced villin expression in HEECs, as did chronic acid exposure, which can be effectively inhibited by Noggin, a specific antagonist of BMP4. Results from a Western blot assay suggest that BMP4 induces activation of smad1 and promotes protein expression of ID2 and CDX2.


CONCLUSIONS
BMP4 may play an important role in the development of BE.
Zhou
Gang
G
Department of Gastroenterology, Southwest Hospital, The Third Military Medical University, ChongQing, China.
Sun
Yong-Gang
YG
Wang
Hong-Bin
HB
Wang
Wei-Qiang
WQ
Wang
Xing-Wei
XW
Fang
Dian-Chun
DC
D000328:Adult; D001471:Barrett Esophagus / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis*; D004947:Esophagus / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
C525809:BMP4 protein, human; D001647:Bile Acids and Salts; D055415:Bone Morphogenetic Protein 4