Regulation of Gastric Epithelial Cell Homeostasis by Gastrin and Bone Morphogenetic Protein Signaling

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.

Role of Different Hormones in the Pathogenesis and Severity of Adolescent Idiopathic Scoliosis

“…Recent studies in rats suggest that gastrin may assist in regulation of bone metabolism, and that higher gastrin levels may contribute to poorer bone quality. 9 , 10 Although gastrin is present at normal levels in most patients, we found a low inverse correlation between gastrin values and the SRS-30 score, which may indicate that the most serious cases have higher serum gastrin levels. Since this is the first study correlating scoliosis and gastrin levels, further studies are required to better clarify this finding.…”

“…Several studies have evaluated the action of gastrin, a peptide hormone produced by G cells of the gastric antrum, in metabolism and bone quality. 9 , 10 Also considering the importance of 25-hydroxyvitamin D (25-OHD) and cortisol in bone metabolism, we seek to correlate the levels of these markers with AIS, the severity of the curve, and the results obtained using the SRS-30 questionnaire.…”

Regulation of Gastric Metaplasia, Dysplasia, and Neoplasia by Bone Morphogenetic Protein Signaling

“… 38 , 39 , 40 The crucial role of gastrin in the expression of the proliferative changes of the noggin transgenic mice was further supported by the observation that crossing of noggin transgenic mice to gastrin knockout mice leads to inhibition of cell proliferation. 41 …”