Mesenchymal transcription factor Fkh6 is essential for the development and differentiation of parietal cells

被引:14
作者
Fukamachi, H
Fukuda, K
Suzuki, M
Furumoto, T
Ichinose, M
Shimizu, S
Tsuchiya, S
Horie, S
Suzuki, Y
Saito, Y
Watanabe, K
Taniguchi, M
Koseki, H
机构
[1] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, Tokyo 1130033, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, Tokyo 1130033, Japan
[3] Chiba Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Chiba 2608670, Japan
[4] Chiba Univ, Fac Pharmaceut Sci, Chem Pharmacol Lab, Inage Ku, Chiba 2630022, Japan
[5] Showa Hosp, Dept Pathol, Kodaira, Tokyo 1878510, Japan
[6] Chiba Univ, Sch Med, JST, CREST,Chuo Ku, Chiba 2608670, Japan
[7] Chiba Univ, Grad Sch Med, Dept Mol Immunol, Chuo Ku, Chiba 2608670, Japan
关键词
Fkh6; stomach; parietal cells; gastric acid; gene targeting; pepsinogen; oxynticopeptic cells; epithelial-mesenchymal interaction; differentiation; evolution;
D O I
10.1006/bbrc.2001.4247
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The role of transcription factor forkhead homologue 6 (Fkh6) gene expressed only in gastrointestinal mesenchymes on the differentiation of gastric epithelia was analyzed by inactivating the gene by targeting disruption. Gastric mucosa exhibited hyperplasias with disordered glandular structures in the absence of gene. Measurement of acid secretion in the isolated whole stomach demonstrated that both basal and stimulated secretions were severely suppressed in the Fkh6-/- stomach, while immunohistochemical studies showed that comparable numbers of parietal cells were differentiated in both wild-type and Fhh6-/- stomachs. Ultrastructurally Fkh6-/- parietal cells were furnished with developed intracellular canaliculi and many mitochondria, but their canaluculi were not enlarged nor fully connected to the luminal surface even when animals were treated with histamine, suggesting that Fkh6-/- parietal cells were far less responsive to acid secretion-inducing stimulations. Some parietal cells contained secretory granules positively stained with anti-pepsinogen antibodies, indicating that they retained characteristics of oxynticopeptic cells found in lower vertebrates. We thus concluded that Fkh6 plays essential roles for the development and differentiation of parietal cells via epithelial-mesenchymal interactions. (C) 2001 Academic Press.
引用
收藏
页码:1069 / 1076
页数:8
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