Research article summary (published 6 Dec 2006):

Bone morphogenetic protein 2 induced differentiation toward superficial epithelial cells in the gastric mucosa.

Full 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.

Author information

Author/s: Itoh, Keisuke (K); Kataoka, Hiromi (H); Sasaki, Makoto (M); Tanida, Satoshi (S); Oshima, Tadayuki (T); Ogasawara, Naotaka (N); Ohara, Hirotaka (H); Nakao, Haruhisa (H); Joh, Takashi (T);

Affiliation: Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Nagoya, 467-8601, Japan.

Journal and publication information

Publication Type: Journal Article

Journal: Journal of gastroenterology (J Gastroenterol), published in Japan. (Language: eng)

Reference: 2006-Nov; vol 41 (issue 11) : pp 1064-75

Dates: Created 2006/12/12; Completed 2007/02/08; Revised 2008/11/21;

PMID: 17160517, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Blotting, Western Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins - genetics; pharmacology Cell Differentiation - drug effects; genetics Cell Line Epithelial Cells - cytology; drug effects Fibroblasts - cytology; drug effects

Fluorescent Antibody Technique Gastric Mucosa - cytology; drug effects Gene Expression Mice Mice, Inbred BALB C RNA, Messenger - genetics Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta - genetics; pharmacology

Associated Chemicals: Bmp2 protein, mouse (0) ; Bone Morphogenetic Protein 2 (0) ; Bone Morphogenetic Proteins (0) ; RNA, Messenger (0) ; Transforming Growth Factor beta (0)

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