Regulation of gastric epithelial cell homeostasis by gastrin and bone morphogenetic protein signaling

Physiological Reports

Andrea Todisco¹  Maria Mao¹  Theresa M. Keeley²  Wei Ye¹  Linda C. Samuelson² 

[1] Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan;Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, Michigan

关键词: Cellular differentiation;    cellular proliferation;    chief cells;    parietal cells;   

DOI  :  10.14814/phy2.12501

来源: Wiley

【 摘 要 】

Abstract

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 (NogTG mice). Three-month-old NogTG mice were crossed to gastrin-deficient (GasKO mice) to generate NogTG;GasKO mice. Morphology of the corpus of wild type, NogTG, GasKO, and NogTG;GasKO mice was analyzed by H&E staining. Distribution of PCs and zymogenic cells (ZCs) was analyzed by immunostaining for the H⁺/K⁺-ATPase and intrinsic factor (IF). Expression of the H⁺/K⁺-ATPase 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 NogTG;GasKO mice displayed a marked reduction in the number of PCs and ZCs in comparison to NogTG mice. Further, cellular proliferation was significantly lower in NogTG;GasKO mice, than in the NogTG 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.

【 授权许可】

CC BY   
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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