Helicobacter pylori Eradication Reverses DNA Damage Response Pathway but Not Senescence in Human Gastric Epithelium.

Abstract

Helicobacter pylori (H. pylori) infection induces DNA Double-Strand Breaks (DSBs) and consequently activates the DNA Damage Response pathway (DDR) and senescence in gastric epithelium. We studied DDR activation and senescence before and after the eradication of the pathogen. Gastric antral and corpus biopsies of 61 patients with H. pylori infection, prior to and after eradication treatment, were analyzed by means of immunohistochemistry/immunofluorescence for DDR marker (γH2AΧ, phosporylated ataxia telangiectasia-mutated (pATM), p53-binding protein (53BP1) and p53) expression. Samples were also evaluated for Ki67 (proliferation index), cleaved caspase-3 (apoptotic index) and GL13 staining (cellular senescence). Ten H. pylori (-) dyspeptic patients served as controls. All patients were re-endoscoped in 72-1361 days (mean value 434 days), and tissue samples were processed in the same manner. The eradication of the microorganism, in human gastric mucosa, downregulates γH2AΧ expression in both the antrum and corpus (p = 0.00019 and p = 0.00081 respectively). The expression of pATM, p53 and 53BP1 is also reduced after eradication. Proliferation and apoptotic indices were reduced, albeit not significantly, after pathogen clearance. Moreover, cellular senescence is increased in H. pylori-infected mucosa and remains unaffected after eradication. Interestingly, senescence was statistically increased in areas of intestinal metaplasia (IM) compared with adjacent non-metaplastic mucosa (p < 0.001). In conclusion, H. pylori infection triggers DSBs, DDR and senescence in the gastric epithelium. Pathogen eradication reverses the DDR activation but not senescence. Increased senescent cells may favor IM persistence, thus potentially contributing to gastric carcinogenesis.

• Authors: Polyxeni Kalisperati, Evangelia Spanou, Ioannis S Pateras, Konstantinos Evangelou, Irene Thymara, Penelope Korkolopoulou, Athanassios Kotsinas, Panayiotis G Vlachoyiannopoulos, Athanasios G Tzioufas, Christos Kanellopoulos, Vassilis G Gorgoulis, Stavros Sougioultzis
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 25 Issue 7 (Mar 31 2024) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 38612698 (Publication Type: Journal Article)

Chemical References

• Tumor Suppressor Protein p53

Topics

• Humans
• Helicobacter pylori
• Tumor Suppressor Protein p53 (genetics)
• Gastric Mucosa
• DNA Repair
• Epithelium