Bone morphogenetic protein 2 induced differentiation toward superficial epithelial cells in the gastric mucosa.
J Gastroenterol
; 41(11): 1064-75, 2006 Nov.
Article
in En
| MEDLINE
| ID: mdl-17160517
ABSTRACT
BACKGROUND:
Epithelial-mesenchymal interactions are important for maintenance of the gastrointestinal tract mucosa. Moreover, diffusible factors from the underlying mesenchyme control the proliferation and differentiation of the epithelial cells. However, the details of the associated signaling remain unknown.METHODS:
Two novel cell lines, designated MSE1 (mouse stomach epithelium) and MSMF1 (mouse stomach myofibroblast) cells, were established from mouse glandular stomach and cocultured in three-dimensional collagen gels in vitro.RESULTS:
MSE1 cells formed dramatic branching tubular structures upon coculture with MSMF1 cells. In contrast, they formed spherical cyst structures in the absence of fibroblast support or the presence of Swiss 3T3 cells. Since bone morphogenetic protein 2 (BMP2) was expressed by MSMF1 cells but not Swiss 3T3 cells, we investigated whether it induced the morphological differentiation. Addition of BMP2 to MSE1 cells induced the formation of branching tubular structures, even in the absence of MSMF1 cells. Noggin, a BMP2 antagonist, blocked the MSMF1-induced tubular branch formation by MSE1 cells. MSE1 cells were induced to express mRNA of MUC5AC, an important marker for gastric superficial epithelium in the upper part of pits, upon branching tubule formation after BMP2 addition. Coculture with MSMF1 cells or BMP2 addition induced Smad1 phosphorylation in MSE1 cells. Furthermore, BMP2 inhibited MSE1 cell proliferation in MTS assays and suppressed AKT phosphorylation.CONCLUSIONS:
BMP2 stimulated MSE1 cells to form branching duct-like structures and differentiate toward superficial epithelium in three-dimensional cocultures in vitro, suggesting that it may act as a morphogen and differentiation inducer in epithelial-mesenchymal interactions of gastric mucosa.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Gene Expression
/
Cell Differentiation
/
Transforming Growth Factor beta
/
Bone Morphogenetic Proteins
/
Epithelial Cells
/
Gastric Mucosa
Limits:
Animals
Language:
En
Journal:
J Gastroenterol
Journal subject:
GASTROENTEROLOGIA
Year:
2006
Document type:
Article
Affiliation country:
Japón