H. Pylori-Facilitated TERT/Wnt/β-Catenin Triggers Spasmolytic Polypeptide-Expressing Metaplasia and Oxyntic Atrophy.

Autor: He L; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Zhang X; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.; Cancer Center of Daping Hospital, Army Medical University, Chongqing, 400000, China., Zhang S; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.; Department of Gastroenterology, The 987th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China, Baoji, Shaanxi, 721000, China., Wang Y; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.; Biological Science Research Center, Southwest University, Chongqing, 400715, China., Hu W; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Li J; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Liu Y; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Liao Y; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Peng X; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Li J; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Zhao H; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Wang L; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.; Central Laboratory, Army Medical University, Chongqing, 400038, China., Lv YF; Department of Pathology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Hu CJ; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China., Yang SM; Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Nov 25, pp. e2401227. Date of Electronic Publication: 2024 Nov 25.
DOI: 10.1002/advs.202401227
Abstrakt: 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.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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