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Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis
BACKGROUND & AIMS: The association between cellular senescence and Helicobacter pylori–induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori–induced atrophic gastritis and the underlying mechanism. METHODS: C57BL/6J mice were infected with H pylori...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859172/ https://www.ncbi.nlm.nih.gov/pubmed/33161156 http://dx.doi.org/10.1016/j.jcmgh.2020.10.015 |
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author | Cai, Qinbo Shi, Peng Yuan, Yujie Peng, Jianjun Ou, Xinde Zhou, Wen Li, Jin Su, Taiqiang Lin, Liangliang Cai, Shirong He, Yulong Xu, Jianbo |
author_facet | Cai, Qinbo Shi, Peng Yuan, Yujie Peng, Jianjun Ou, Xinde Zhou, Wen Li, Jin Su, Taiqiang Lin, Liangliang Cai, Shirong He, Yulong Xu, Jianbo |
author_sort | Cai, Qinbo |
collection | PubMed |
description | BACKGROUND & AIMS: The association between cellular senescence and Helicobacter pylori–induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori–induced atrophic gastritis and the underlying mechanism. METHODS: C57BL/6J mice were infected with H pylori for biological and mechanistic studies in vivo. Gastric precancerous lesions from patients and mouse models were collected and analyzed using senescence-associated beta-galactosidase, Sudan Black B, and immunohistochemical staining to analyze senescent cells, signaling pathways, and H pylori infection. Chromatin immunoprecipitation, luciferase reporter assays, and other techniques were used to explore the underlying mechanism in vitro. RESULTS: Gastric mucosa atrophy was highly associated with cellular senescence. H pylori promoted gastric epithelial cell senescence in vitro and in vivo in a manner that depended on C-X-C motif chemokine receptor 2 (CXCR2) signaling. Interestingly, H pylori infection not only up-regulated the expression of CXCR2 ligands, C-X-C motif chemokine ligands 1 and 8, but also transcriptionally up-regulated the expression of CXCR2 via the nuclear factor-κB subunit 1 directly. In addition, CXCR2 formed a positive feedback loop with p53 to continually enhance senescence. Pharmaceutical inhibition of CXCR2 in an H pylori–infected mouse model attenuated mucosal senescence and atrophy, and delayed further precancerous lesion progression. CONCLUSIONS: Our study showed a new mechanism of H pylori–induced atrophic gastritis through CXCR2-mediated cellular senescence. Inhibition of CXCR2 signaling is suggested as a potential preventive therapy for targeting H pylori–induced atrophic gastritis. GEO data set accession numbers: GSE47797 and GSE3556. |
format | Online Article Text |
id | pubmed-7859172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78591722021-02-05 Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis Cai, Qinbo Shi, Peng Yuan, Yujie Peng, Jianjun Ou, Xinde Zhou, Wen Li, Jin Su, Taiqiang Lin, Liangliang Cai, Shirong He, Yulong Xu, Jianbo Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: The association between cellular senescence and Helicobacter pylori–induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori–induced atrophic gastritis and the underlying mechanism. METHODS: C57BL/6J mice were infected with H pylori for biological and mechanistic studies in vivo. Gastric precancerous lesions from patients and mouse models were collected and analyzed using senescence-associated beta-galactosidase, Sudan Black B, and immunohistochemical staining to analyze senescent cells, signaling pathways, and H pylori infection. Chromatin immunoprecipitation, luciferase reporter assays, and other techniques were used to explore the underlying mechanism in vitro. RESULTS: Gastric mucosa atrophy was highly associated with cellular senescence. H pylori promoted gastric epithelial cell senescence in vitro and in vivo in a manner that depended on C-X-C motif chemokine receptor 2 (CXCR2) signaling. Interestingly, H pylori infection not only up-regulated the expression of CXCR2 ligands, C-X-C motif chemokine ligands 1 and 8, but also transcriptionally up-regulated the expression of CXCR2 via the nuclear factor-κB subunit 1 directly. In addition, CXCR2 formed a positive feedback loop with p53 to continually enhance senescence. Pharmaceutical inhibition of CXCR2 in an H pylori–infected mouse model attenuated mucosal senescence and atrophy, and delayed further precancerous lesion progression. CONCLUSIONS: Our study showed a new mechanism of H pylori–induced atrophic gastritis through CXCR2-mediated cellular senescence. Inhibition of CXCR2 signaling is suggested as a potential preventive therapy for targeting H pylori–induced atrophic gastritis. GEO data set accession numbers: GSE47797 and GSE3556. Elsevier 2020-11-05 /pmc/articles/PMC7859172/ /pubmed/33161156 http://dx.doi.org/10.1016/j.jcmgh.2020.10.015 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Cai, Qinbo Shi, Peng Yuan, Yujie Peng, Jianjun Ou, Xinde Zhou, Wen Li, Jin Su, Taiqiang Lin, Liangliang Cai, Shirong He, Yulong Xu, Jianbo Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis |
title | Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis |
title_full | Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis |
title_fullStr | Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis |
title_full_unstemmed | Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis |
title_short | Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis |
title_sort | inflammation-associated senescence promotes helicobacter pylori–induced atrophic gastritis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859172/ https://www.ncbi.nlm.nih.gov/pubmed/33161156 http://dx.doi.org/10.1016/j.jcmgh.2020.10.015 |
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