Dynamic characterization of intestinal metaplasia in the gastric corpus mucosa of Atp4a-deficient mice
| العنوان: | Dynamic characterization of intestinal metaplasia in the gastric corpus mucosa of Atp4a-deficient mice |
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| المؤلفون: | Yan Yan, Zi-ming Zhao, Yuan-liang Liu, Huafeng Pan, Wei Liu, Dongsheng Yuan, Qi Wang, Liangjun Yang |
| المصدر: | Bioscience Reports |
| بيانات النشر: | Portland Press Ltd., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Time Factors, Cellular homeostasis, Mucin 2, Achlorhydria, Biochemistry, Molecular Bases of Health & Disease, structure-function, H(+)-K(+)-Exchanging ATPase, 0302 clinical medicine, Research Articles, Parietal cell, Mice, Knockout, education.field_of_study, Chemistry, TOR Serine-Threonine Kinases, H+, Cell Transformation, Neoplastic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biomarker, Signal Transduction, Lactate dehydrogenase A, Biophysics, 03 medical and health sciences, atrophy, dysplasia, Parietal Cells, Gastric, Stomach Neoplasms, Gastric mucosa, medicine, Animals, education, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, K+-ATPase, Metaplasia, Mucin-2, Cell Biology, medicine.disease, Molecular biology, Signaling, Mice, Inbred C57BL, Metabolism, 030104 developmental biology, Chronic Disease, Warburg effect, Phosphatidylinositol 3-Kinase, Energy Metabolism, Precancerous Conditions, Proto-Oncogene Proteins c-akt, Developmental Biology |
| الوصف: | Parietal cells of the gastric mucosa contain a complex and extensive secretory membrane system that harbors gastric H+, K+-adenosine triphosphatase (ATPase), the enzyme primarily responsible for gastric lumen acidification. Here, we describe the characterization of mice deficient in the H+, K+-ATPase α subunit (Atp4a−/−) to determine the role of this protein in the biosynthesis of this membrane system and the biology of the gastric mucosa. Atp4a−/− mice were produced by gene targeting. Wild-type (WT) and Atp4a−/− mice, paired for age, were examined at 10, 12, 14 and 16 weeks for histopathology, and the expression of mucin 2 (MUC2), α-methylacyl-CoA racemase (AMACR), Ki-67 and p53 proteins was analyzed by immunohistochemistry. For further information, phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-AKT), mechanistic target of rapamycin (mTOR), hypoxia-inducible factor 1α (HIF-1α), lactate dehydrogenase A (LDHA) and sirtuin 6 (SIRT6) were detected by Western blotting. Compared with the WT mice, hypochlorhydric Atp4a−/− mice developed parietal cell atrophy and significant antral inflammation (lymphocyte infiltration) and intestinal metaplasia (IM) with elevated MUC2 expression. Areas of dysplasia in the Atp4a−/− mouse stomach showed increased AMACR and Ki-67 expression. Consistent with elevated antral proliferation, tissue isolated from Atp4a−/− mice showed elevated p53 expression. Next, we examined the mechanism by which the deficiency of the H+, K+-ATPase α subunit has an effect on the gastric mucosa. We found that the expression of phosphorylated-PI3K, p-AKT, phosphorylated-mTOR, HIF-1α, LDHA and SIRT6 was significantly higher in tissue from the Atp4a−/− mice compared with the WT mice (P |
| تدمد: | 1573-4935 0144-8463 |
| DOI: | 10.1042/bsr20181881 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c0d64acad408f72363425d3d444be95 https://doi.org/10.1042/bsr20181881 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0c0d64acad408f72363425d3d444be95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15734935 01448463 |
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| DOI: | 10.1042/bsr20181881 |