Altered Mucin Expression in the Gastric Epithelium After Injury and Regeneration May Result in Increased Helicobacter pylori‐Induced Gastric Ulcers in the Elderly
Authors: Dua‐Awereh Martha B. , Chakrabarti Jayati , Goker Sevde , Engevik Amy , Hawkins Jennifer , Helmrath Michael , Zavros Yana 
Published: June 2021

Background/Hypothesis

Prevalence of gastric ulcers increase in the elderly, yet the cause of the age‐associated escalation is unknown. Once Helicobacter pylori (H. pylori) enters the stomach lumen, bacterial urease not only converts water & urea to ammonia & bicarbonate to neutralize the acidic environment of the stomach, but also breaks down the protective mucous barrier by breaking down mucin. Subsequently, chronic inflammation induced by H. pylori infection results in epithelial cell death and damage to the stomach lining, also known as a gastric ulcer. We tested the hypothesis that the regenerative process of the aged gastric epithelium is impaired in response to injury, such that there is mis‐localization of mucin expression leading to a compromised protective barrier.

Methods

Gastric ulcers were induced in young (2–3 months old) and aged (>8 months old) C57/BL6 mice with acetic acid applied on the serosal side of the stomach. Samples were harvested from euthanized mice with ulcer durations from 3 to 60 days. Biopsies were collected from human gastric ulcer patients. Organoids were grown from young mouse gastric epithelium and transplanted at the site of acetic acid‐induced injury in aged mice. Immunofluorescence staining was used to analyze the expression of MUC5AC, MUC2, Griffonia simplicifolia II (GSII), Ulex europeus I (UEAI), H+, K+‐ATPase, intrinsic factor and chromogranin A.

Results

Within 3 days post‐injury, there was the emergence of spasmolytic polypeptide‐expressing metaplasia (SPEM) at the ulcer margins of both young and aged gastric epithelium. Sixty days post‐injury there was complete regeneration of the gastric epithelium that exhibited the expression of parietal, chief and endocrine cells, and no evidence of SPEM in the young mice. However, the aged gastric epithelium exhibited the persistence of SPEM glands, expression of MUC2 and gastric cancer stem cell marker CD44v9. Aged mice transplanted with gastric organoids derived from young mice exhibited normal MUC5AC, GSII and UEAI expression similar to young mice 60 days post‐injury. Organoid transplantation of the aged gastric epithelium resulted in the normal expression of gastric cell lineages with an intact mucosal layer.

Conclusions

Following injury in aged gastric tissues, the mucous layer becomes altered such that SPEM persists uncontrolled and there is loss of normal MUC5AC expression and gastric cell lineages. Ongoing experiments include studies of increased susceptibility to H. pylori‐induced metaplasia and cancer development using an in vivo acetic acid‐induced injury mouse model and human‐ and mouse‐derived gastric organoids.

Support or Funding Information

NIH (NIDDK) 5R01DK083402‐08 grant (YZ)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.