H. Pylori ‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy
Abstract: Persistent H. pylori infection triggers the repair program of the mucosa, such as spasmolytic polypeptide‐expressing metaplasia (SPEM). However, the mechanism underlying the initiation of SPEM in gastric tissues by H. pylori remains unclear. Here, an increase in telomerase reverse transcriptase (TERT) protein expression is observed in chief cells upon infection with cagA‐positive H. pylori. Tert knockout significantly ameliorated H. pylori‐induced SPEM and single‐cell RNA sequencing demonstrated that the Wnt/β‐Catenin pathway is suppressed in gastric cells with Tert knockout. Mechanism study revealed that CagA elevated TERT abundance by disrupting the interaction between TERT and its novel E3 ligase, SYVN1. Interestingly, Nitazoxanide effectively relieved SPEM via inhibition of the Wnt/β‐Catenin signaling in vivo. This results clarified the mechanism underlying which CagA activated the TERT/Wnt/β‐Catenin pathway, thus promoting the dedifferentiation of chief cells and the occurrence of SPEM in gastric mucosa. This highlights a molecular basis for targeting CagA‐activated Wnt signaling in chief cells for the treatment of gastric precancerous lesions.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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H. Pylori ‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy ; day:25 ; month:11 ; year:2024 ; extent:16
Advanced science ; (25.11.2024) (gesamt 16)
- Creator
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He, Lijiao
Zhang, Xiao
Zhang, Shengwei
Wang, Yi
Hu, Weichao
Li, Jie
Liu, Yunyi
Liao, Yu
Peng, Xue
Li, Jianjun
Zhao, Haiyan
Wang, Liting
Lv, Yang‐Fan
Hu, Chang‐Jiang
Yang, Shi‐Ming
- DOI
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10.1002/advs.202401227
- URN
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urn:nbn:de:101:1-2411261336569.004548079258
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:32 AM CEST
Data provider
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Associated
- He, Lijiao
- Zhang, Xiao
- Zhang, Shengwei
- Wang, Yi
- Hu, Weichao
- Li, Jie
- Liu, Yunyi
- Liao, Yu
- Peng, Xue
- Li, Jianjun
- Zhao, Haiyan
- Wang, Liting
- Lv, Yang‐Fan
- Hu, Chang‐Jiang
- Yang, Shi‐Ming
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