Gastric achlorhydria in H/K‐ATPase‐deficient (Atp4a(–/–)) mice causes severe hyperplasia, mucocystic metaplasia and upregulation of growth factors

摘要: Background:  Gastric neoplasia is common in humans, yet controversy remains over contributions of chronic achlorhydria, gastrinemia and hyperplasia, to cancer risk. To study this, mice lacking the gastric H/K-ATPase (Atp4a(–/–) mice) were used determine whether loss acid secretion, with attendant hypergastrinemia, predisposes phenotype. Methods: Atp4a(–/–) Atp4a(+/+) mice, paired for age gender, examined at 3, 8, 12 20 months histopathology, expression trefoil factor family (TFF)1–3, Reg IIIβ, γ δ, osteopontin, CD44, chromogranin A, Crp-ductin, galectin, all which are important cell growth. Results:  By 8 months, glandular stomach Atp4a(–/–) doubled weight thickness, several modulators growth increased. Female more hyperplastic than males 20 months. 1 year, severe mucocystic incomplete intestinal metaplasia, ciliated a shift mucins from neutral acidic, inflammation widespread. Cells mucus pit zone developed pyloric-type appearance, containing large hyaline-like, periodic acid–Schiff (PAS)-negative/alcian blue-negative inclusions. But critical characteristics neoplasia, such as nuclear atypia, invasion into muscularis mucosa, metastases absent. In A histidine decarboxylase, RegIIIγ TFF3, osteopontin CD44 upregulated while TFF1 reduced. Conclusions:  Chronic achlorhydria hypergastrinemia aged produced progressive upregulation factors without histological evidence neoplasia. © 2005 Blackwell Publishing Asia Pty Ltd