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Herein, we explore the role of sphingosine\u20101\u2010phosphate receptor\u20102 (S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor) in mediating the development of chronic gastritis, as well as the effect of S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonists in attenuating its development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Chronic gastritis model was established through long\u2010term exposure to lipopolysaccharide (LPS) in mice. S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonists were administrated via gavage. Western blotting and immunohistochemistry assays analysed S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor and paralemmin\u20103 (PALM3). Co\u2010immunoprecipitation and immunofluorescence staining assays identified the binding of S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor with NF\u2010kappa\u2010B\u2010activating protein (NKAP) or PALM3 in the nuclei. Haematoxylin\u2013eosin staining assessed gastric tissues. 16S ribosomal RNA gene amplicon sequencing analysed gastric microbiota compositions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Long\u2010term exposure to LPS developed chronic gastritis by activating S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptors in gastric epithelial cells. Mechanistically, LPS stimulated PALM3\u2010mediated nuclear translocation of S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptors, which then bound to NKAP; leading to the upregulation of NF\u2010\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B\/IL\u20106 pathway. Inhibition of S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptors blocked LPS\u2010induced nuclear translocation, resulting in downregulation of NF\u2010\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B\/IL\u20106 pathway. Administration of S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonists attenuated the LPS\u2010induced chronic gastritis. Additionally, abundance of pathogenic Gram\u2010negative gastric bacteria (e.g.,\n                      <jats:italic>Enterobacter<\/jats:italic>\n                      ) was significantly reduced following treatment with S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonists.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      Long\u2010term exposure to LPS developed chronic gastritis by stimulating S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptors. S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptors thus represent a potential target for treatment of chronic gastritis. S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonist blocks the LPS\u2010induced nuclear translocation of S1P\n                      <jats:sub>2<\/jats:sub>\n                      receptors, thus attenuating chronic gastritis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70323","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T05:55:20Z","timestamp":1767160520000},"page":"2273-2286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of sphingosine\u20101\u2010phosphate receptor\u20102 attenuates chronic gastritis via blocking nuclear translocation of S1P\n                    <sub>2<\/sub>\n                    receptors in epithelial cells"],"prefix":"10.1111","volume":"183","author":[{"given":"Ke\u2010Qin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Capital Medical University  Beijing China"},{"name":"Department of Clinical Pharmacy Beijing Electric Power Hospital of State Grid Co. of China, Capital Medical University Electric Teaching Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Meng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Bing","family":"Shao","sequence":"additional","affiliation":[{"name":"Toxicology and Sanitary Chemistry, School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Yong","family":"Tan","sequence":"additional","affiliation":[{"name":"Toxicology and Sanitary Chemistry, School of Public Health Capital Medical University  Beijing 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