{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:45:09Z","timestamp":1789101909878,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971489"],"award-info":[{"award-number":["81971489"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671571"],"award-info":[{"award-number":["81671571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2025,5]]},"abstract":"ABSTRACT<\/jats:title>Background<\/jats:title>Helicobacter pylori<\/jats:italic><\/jats:styled-content> (H. pylori<\/jats:italic><\/jats:styled-content>) infection is one of the most important risk factors for chronic gastritis, gastric ulcers, and gastric cancer. Mast cells act as a crucial regulator in bacterial infection. The mechanisms underlying mast cell activation and their role in H. pylori<\/jats:italic><\/jats:styled-content> infection remain poorly understood.<\/jats:p><\/jats:sec>Materials and Methods<\/jats:title>In gastric mucosal tissue, the number of mast cells, G\u2010protein\u2010coupled receptor 171 (GPR171) and CCL2 expression were detected by immunohistochemistry (IHC) or immunofluorescence between H. pylori<\/jats:italic><\/jats:styled-content>\u2010negative and H.\u00a0pylori<\/jats:italic><\/jats:styled-content>\u2010positive patients. Mast cells were co\u2010cultured with H. pylori<\/jats:italic><\/jats:styled-content>, and transcriptome sequencing, RT\u2010qPCR, and Western blotting (WB) were performed to identify receptors involved in mast cell activation. WB, chromatin immunoprecipitation (ChIP), and dual\u2010luciferase reporter assays were conducted to investigate the molecular mechanism by which HIF\u20101\u03b1 regulates GPR171 expression. Lentiviral knockdown, ELISA, WB, and IHC were used to evaluate the role of GPR171 during H. pylori<\/jats:italic><\/jats:styled-content> infection. An in\u00a0vivo mouse model of H. pylori<\/jats:italic><\/jats:styled-content> infection was employed to assess the effects of GPR171 blockade on CCL2 expression and gastric mucosal inflammation.<\/jats:p><\/jats:sec>Results<\/jats:title>In the study, we found that mast cell numbers were greatly increased and correlated with the severity of inflammation in H. pylori<\/jats:styled-content>\u2010<\/jats:italic>infected patients. We found a new receptor, GPR171, was upregulated and involved in mast cell activation upon H.\u00a0pylori<\/jats:italic><\/jats:styled-content> infection. Furthermore, H. pylori<\/jats:italic><\/jats:styled-content> infection induced the expression of GPR171 by promoting the activation of hypoxia\u2010inducible factor 1 alpha (HIF\u20101\u03b1), which directly bound to hypoxia response elements in the GPR171 promoter and regulated its transcriptional activity. Blockade or loss of GPR171 in mast cells partially inhibited CCL2 secretion via the ERK1\/2 signaling pathway. In the human gastric mucosa, CCL2 derived from mast cells was associated with gastric inflammation during H. pylori<\/jats:italic><\/jats:styled-content> infection. In\u00a0vivo murine studies indicated that H. pylori<\/jats:italic><\/jats:styled-content> infection significantly upregulated CCL2 expression, while GPR171 inhibition partially reduced CCL2 levels and alleviated gastric mucosal inflammation.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>We provide a novel mechanism that H. pylori<\/jats:italic><\/jats:styled-content> activates mast cells to promote gastric inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.70042","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:44:37Z","timestamp":1746405877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["HIF<\/scp>\u20101\u03b1\u2010Induced GPR171<\/scp> Expression Mediates CCL2<\/scp> Secretion by Mast Cells to Promote Gastric Inflammation During Helicobacter pylori<\/i> Infection"],"prefix":"10.1111","volume":"30","author":[{"given":"Hanmei","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The Eighth Affiliated Hospital Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Eighth Affiliated Hospital Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Eighth Affiliated Hospital Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Eighth Affiliated Hospital Sun Yat\u2010Sen University Shenzhen 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