{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:34:56Z","timestamp":1786980896765,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["23590664"],"award-info":[{"award-number":["23590664"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012314","name":"Shinshu University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012314","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dig Dis Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sessile serrated lesions (SSLs) are recognized as precursors in the serrated neoplastic pathway leading to microsatellite instability-high colorectal cancer. A hallmark feature of SSLs on endoscopic examination is the mucous cap.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to investigate the expression of the bicarbonate transporters SLC26A3 and CFTR in SSLs, using immunohistochemistry to elucidate their potential involvement in the pathogenesis of mucous cap formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed 14 SSLs from 12 patients using formalin-fixed, paraffin-embedded tissue sections. Histochemical staining with high-iron diamine-Alcian blue (HID-AB) and immunohistochemistry for MUC2, MUC5AC, SLC26A3, and CFTR were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In normal colonic mucosa, MUC2 was strongly expressed in goblet cells, whereas MUC5AC was absent. SLC26A3 was expressed on the apical membrane and in the cytoplasm of surface epithelial and upper crypt cells, while CFTR was localized to the apical membrane of epithelial cells along the crypt axis. In SSLs, crypts showed architectural distortion with mucin retention in the dilated lumina and an overlying mucous cap. HID-AB staining revealed the presence of sulfomucins and sialomucins. Goblet cells coexpressed MUC2 and MUC5AC, with MUC2 showing broader and stronger expression. These mucins showed a partially distinct and mutually exclusive distribution. Notably, SLC26A3 and CFTR expression levels were markedly reduced or absent in SSLs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SSLs showed a mixed acidic mucin phenotype and downregulated epithelial bicarbonate transporters. This may impair mucin expansion and hydration, leading to the formation of adhesive mucous caps, showing the potential link between defective bicarbonate transport and mucin physiology in SSLs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10620-025-09470-5","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:56:34Z","timestamp":1760720194000},"page":"941-947","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impaired Bicarbonate Transport via SLC26A3 and CFTR Downregulation Promotes Mucous Cap Formation in Sessile Serrated Lesions"],"prefix":"10.1007","volume":"71","author":[{"given":"Hiroyoshi","family":"Ota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miharu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiwa","family":"Tanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Kusama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuo","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Uehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"9470_CR1","unstructured":"Pai R, M\u00e4kinen M, Rosty C. Colorectal serrated lesions and polyps. In: the WHO classification of tumours editorial bord (ed) WHO Classification of Tumours Digestive System Tumours, Lyon (France); International Agency for Research on Cancer (IARC). 2019;163\u2013169. http:\/\/publications.iarc.fr\/579."},{"key":"9470_CR2","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1016\/j.gie.2011.08.008","volume":"74","author":"US Tadepalli","year":"2011","unstructured":"Tadepalli US, Feihel D, Miller KM, Itzkowitz SH, Freedman JS, Kornacki S, Cohen LB, Bamji ND, Bodian CA, Aisenberg J. A morphologic analysis of sessile serrated polyps observed during routine colonoscopy (with video). 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