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 transcrip...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202401227 |
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| author | Lijiao He Xiao Zhang Shengwei Zhang Yi Wang Weichao Hu Jie Li Yunyi Liu Yu Liao Xue Peng Jianjun Li Haiyan Zhao Liting Wang Yang‐Fan Lv Chang‐Jiang Hu Shi‐Ming Yang |
| author_facet | Lijiao He Xiao Zhang Shengwei Zhang Yi Wang Weichao Hu Jie Li Yunyi Liu Yu Liao Xue Peng Jianjun Li Haiyan Zhao Liting Wang Yang‐Fan Lv Chang‐Jiang Hu Shi‐Ming Yang |
| author_sort | Lijiao He |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3dc5e45b1b5644eb9090f094d0c32f95 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-3dc5e45b1b5644eb9090f094d0c32f952025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202401227H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic AtrophyLijiao He0Xiao Zhang1Shengwei Zhang2Yi Wang3Weichao Hu4Jie Li5Yunyi Liu6Yu Liao7Xue Peng8Jianjun Li9Haiyan Zhao10Liting Wang11Yang‐Fan Lv12Chang‐Jiang Hu13Shi‐Ming Yang14Department of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Pathology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaDepartment of Gastroenterology The Second Affiliated Hospital of Army Medical University Chongqing 400037 ChinaAbstract 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.https://doi.org/10.1002/advs.202401227CagAH. pylori infectionnitazoxanideSPEMTERT |
| spellingShingle | Lijiao He Xiao Zhang Shengwei Zhang Yi Wang Weichao Hu Jie Li Yunyi Liu Yu Liao Xue Peng Jianjun Li Haiyan Zhao Liting Wang Yang‐Fan Lv Chang‐Jiang Hu Shi‐Ming Yang H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy Advanced Science CagA H. pylori infection nitazoxanide SPEM TERT |
| title | H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy |
| title_full | H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy |
| title_fullStr | H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy |
| title_full_unstemmed | H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy |
| title_short | H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy |
| title_sort | h pylori facilitated tert wnt β catenin triggers spasmolytic polypeptide expressing metaplasia and oxyntic atrophy |
| topic | CagA H. pylori infection nitazoxanide SPEM TERT |
| url | https://doi.org/10.1002/advs.202401227 |
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