Open AccessRegulation of gastric epithelial cell homeostasis by gastrin and bone morphogenetic protein signaling
Author(s) -
Todisco Andrea,
Mao Maria,
Keeley Theresa M.,
Ye Wei,
Samuelson Linda C.,
Eaton Kathryn A.
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12501
Subject(s) - noggin , gastrin , biology , bone morphogenetic protein , bmpr2 , microbiology and biotechnology , immunostaining , endocrinology , cell growth , medicine , gastric chief cell , signal transduction , cellular differentiation , gastric mucosa , immunology , secretion , immunohistochemistry , stomach , biochemistry , genetics , gene
We reported that transgenic expression of the bone morphogenetic protein ( BMP ) signaling inhibitor noggin in the mouse stomach, leads to parietal‐cell ( PC ) loss, expansion of transitional cells expressing markers of both mucus neck and zymogenic lineages, and to activation of proliferative mechanisms. Because these cellular changes were associated with increased levels of the hormone gastrin, we investigated if gastrin mediates the expression of the phenotypic changes of the noggin transgenic mice (Nog TG mice). Three‐month‐old Nog TG mice were crossed to gastrin‐deficient (Gas KO mice) to generate Nog TG ;Gas KO mice. Morphology of the corpus of wild type, Nog TG , Gas KO , and Nog TG ;Gas KO mice was analyzed by H&E staining. Distribution of PC s and zymogenic cells ( ZC s) was analyzed by immunostaining for the H + /K + ‐ ATP ase and intrinsic factor ( IF ). Expression of the H + /K + ‐ ATP ase and IF genes and proteins were measured by QRT ‐ PCR and western blots. Cell proliferation was assessed by immunostaining for proliferating cell nuclear antigen. The corpus of the Nog TG ;Gas KO mice displayed a marked reduction in the number of PC s and ZC s in comparison to Nog TG mice. Further, cellular proliferation was significantly lower in Nog TG ;Gas KO mice, than in the Nog TG mice. Thus, gastrin mediates the increase in gastric epithelial cell proliferation induced by inhibition of BMP signaling in vivo. Moreover, gastrin and BMP signaling exert cooperative effects on the maturation and differentiation of both the zymogenic and PC lineages. These findings contribute to a better understanding of the factors involved in the control of gastric epithelial cell homeostasis.