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Studies have shown that anion secretion via the cystic fibrosis conductance regulator (Cftr) regulates mucus formation in the small intestine. However, mechanisms regulating mucus formation in the colon are less understood. The aim of this study was to explore the role of anion transport in the regulation of mucus formation during steady state and in response to carbamylcholine (CCh) and prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ). The broad-spectrum anion transport inhibitor 4,4\u2032-diisothiocyanatostilbene-2,2\u2032-disulfonate (DIDS), CftrdF508 (CF) mice, and the slc26a3 inhibitor SLC26A3-IN-2 were used to inhibit anion transport. In the distal colon, steady-state mucus expansion was reduced by SLC26A3-IN-2 and normal in CF mice. PGE\n                    <jats:sub>2<\/jats:sub>\n                    stimulated mucus expansion without de novo mucus release in wild type (WT) and CF colon via slc26a3 sensitive mechanisms, while CCh induced de novo mucus secretion in WT but not in CF colon. However, when added simultaneously, CCh and PGE\n                    <jats:sub>2<\/jats:sub>\n                    stimulated de novo mucus secretion in the CF colon via DIDS-sensitive pathways. A similar response was observed in CF ileum that responded to CCh and PGE\n                    <jats:sub>2<\/jats:sub>\n                    with DIDS-sensitive de novo mucus secretion. In conclusion, this study suggests that slc26a3 regulates colonic mucus expansion, while Cftr regulates CCh-induced de novo mucus secretion from ileal and distal colon crypts. Furthermore, these findings demonstrate that in the absence of a functional Cftr channel, parallel stimulation with CCh and PGE\n                    <jats:sub>2<\/jats:sub>\n                    activates additional anion transport processes that help release mucus from intestinal goblet cells.\n                  <\/jats:p>","DOI":"10.1007\/s00424-024-02975-4","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T02:02:28Z","timestamp":1717380148000},"page":"1209-1219","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The anion exchanger slc26a3 regulates colonic mucus expansion during steady state and in response to prostaglandin E2, while Cftr regulates de novo mucus release in response to carbamylcholine"],"prefix":"10.1007","volume":"476","author":[{"given":"Penny L.","family":"Ljungholm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ermund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly M.","family":"S\u00f6derlund Garsveden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor L.","family":"Pettersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-4065","authenticated-orcid":false,"given":"Jenny K.","family":"Gustafsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"2975_CR1","doi-asserted-by":"crossref","unstructured":"Ambort D et al (2012) Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. 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