{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:53:54Z","timestamp":1785322434497,"version":"3.55.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"japan society for the promotion of science","doi-asserted-by":"publisher","award":["Grants-in-Aid for Scientific Research nos. 16K08708 (MK), 17K17779 (HKo), and 15H04712 (JN)"],"award-info":[{"award-number":["Grants-in-Aid for Scientific Research nos. 16K08708 (MK), 17K17779 (HKo), and 15H04712 (JN)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated A4gnt\/ Chst4 double-knockout (DKO) mice by crossing A4gnt knockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with Chst4 KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. A4gnt\/ Chst4 DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in A4gnt\/ Chst4 DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). Cxcl1, Cxcl5, Ccl2, and Cxcr2 transcripts in gastric mucosa of 5-week-old A4gnt\/ Chst4 DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched A4gnt KO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old A4gnt\/ Chst4 DKO mice exhibiting high-grade dysplasia\/adenocarcinoma and GCP. Moreover, Cxcl1 and Cxcr2 were downregulated in A4gnt\/ Chst4 DKO mice relative to age-matched A4gnt KO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in A4gnt KO mice by transiently regulating a set of inflammation-related genes, Cxcl1, Cxcl5, Ccl2, and Cxcr2 at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development:<\/jats:p>","DOI":"10.1369\/0022155419860134","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T10:37:24Z","timestamp":1561631844000},"page":"759-770","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Analysis of\n                    <i>A4gnt<\/i>\n                    Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda"],"prefix":"10.1369","volume":"67","author":[{"given":"Masatomo","family":"Kawakubo","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Komura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukinobu","family":"Goso","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chifumi","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Arisaka","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Harumiya","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Yamanoi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenori","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Iiyama Red Cross Hospital, Iiyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kakuta","sequence":"additional","affiliation":[{"name":"Research Center for Human and Environmental Sciences, Shinshu University, Matsumoto, Japan"},{"name":"Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Immunology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko N.","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Tumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA"},{"name":"Laboratory for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Tumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,6,27]]},"reference":[{"key":"bibr1-0022155419860134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/bchm.1998.379.1.1","volume":"379","author":"Nieuw Amerongen AV","year":"1998","journal-title":"Biol Chem"},{"key":"bibr2-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.2343"},{"key":"bibr3-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0302-3"},{"key":"bibr4-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80083-7"},{"key":"bibr5-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00394-4"},{"key":"bibr6-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1038\/ni1259"},{"key":"bibr7-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1038\/ni1258"},{"key":"bibr8-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407503101"},{"key":"bibr9-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01189.x"},{"key":"bibr10-0022155419860134","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/bjc.1969.9","volume":"23","author":"Gad A. A histochemical study of human alimentary tract mucosubstances in health and disease. I","year":"1969","journal-title":"Br J Cancer"},{"key":"bibr11-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-018-1667-8"},{"key":"bibr12-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59087"},{"key":"bibr13-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1177\/13.3.211"},{"key":"bibr14-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311150200"},{"key":"bibr15-0022155419860134","volume":"54","author":"Avey MT","year":"2015","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"bibr16-0022155419860134","first-page":"39","volume-title":"Pathology and genetics of tumours of the digestive system","author":"Fenoglio-Preiser C","year":"2000"},{"key":"bibr17-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.17027"},{"key":"bibr18-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1042\/bj3180409"},{"key":"bibr19-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090667"},{"key":"bibr20-0022155419860134","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.151.5.2399","volume":"151","author":"Fleming TJ","year":"1993","journal-title":"J Immunol"},{"key":"bibr21-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1021\/ja035660t"},{"key":"bibr22-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(10)78001-0"},{"key":"bibr23-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1021\/pr7008252"},{"key":"bibr24-0022155419860134","volume":"1825","author":"Verbeke H","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"bibr25-0022155419860134","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7376"},{"key":"bibr26-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(98)00081-8"},{"key":"bibr27-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0410226"},{"key":"bibr28-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13156"},{"key":"bibr29-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.01.003"},{"key":"bibr30-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1038\/nature07205"},{"key":"bibr31-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.025"},{"key":"bibr32-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.003"},{"key":"bibr33-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1981.tb01817.x"},{"key":"bibr34-0022155419860134","volume":"33","author":"Mitomi H","year":"1998","journal-title":"Scand J Gastroenterol"},{"key":"bibr35-0022155419860134","volume":"81","author":"Fonde EC","year":"1986","journal-title":"Am J Gastroenterol"},{"key":"bibr36-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.075168"},{"key":"bibr37-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011451"},{"key":"bibr38-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604155200"},{"key":"bibr39-0022155419860134","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28551"}],"container-title":["Journal of Histochemistry &amp; Cytochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1369\/0022155419860134","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1369\/0022155419860134","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1369\/0022155419860134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:28:03Z","timestamp":1777501683000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1369\/0022155419860134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,27]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1369\/0022155419860134"],"URL":"https:\/\/doi.org\/10.1369\/0022155419860134","relation":{},"ISSN":["0022-1554","1551-5044"],"issn-type":[{"value":"0022-1554","type":"print"},{"value":"1551-5044","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,27]]}}}