Inflammation-Associated Senescence Promotes Helicobacter pylori–Induced Atrophic Gastritis
Authors: Wen Zhou
Jianbo Xu
Liangliang Lin
Taiqiang Su
Yujie Yuan
Qinbo Cai
Peng Shi
Jianjun Peng
Jin Li
Xinde Ou
Yulong He
Shirong Cai
Journal: Cellular and Molecular Gastroenterology and Hepatology (2021)
Discipline: CLINICAL MEDICINE
Keywords: C-X-C Motif Chemokine Receptor 2; H pylori; Mucosa Atrophy; Senescent Cell.
Affiliations: Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangdong, China; Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangdong, China., Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangdong, China; Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China; Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangdong, China; Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China. Electronic address: ., Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangdong, China. Electronic address: .

Abstract:  Background &amp; 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. 

Retracted: No

PubPeer comments:
 There appears to be a duplicated image in Figure 4G. *** ![file] , 
 Dear Actinopolyspora, Thank you very much for pointing out the mistake of our paper. We have carefully checked the raw data and found that this two duplicated pictures was a mistake of paste during figure assembly. According to the raw data, the picture in Figure 4G-BrdU-H.pylori-#1 was right, while the picture in Figure 4G-BrdU-PBS-#2 was mistakenly used. Please see the right picture after correction below. We regret that we did not catch this error during revisions and proofing processes. We apologize for this any confusion caused by this unintentional error and we are preparing a correction request to the journal sooner. Thank you again for your kindly reminder! Best regards, Jianbo Xu ![file] ,