{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:59:37Z","timestamp":1784563177748,"version":"3.55.0"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011086","name":"North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Foundation","doi-asserted-by":"crossref","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/100011086","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015521","name":"Stanford Maternal Child Health Research Institute","doi-asserted-by":"crossref","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/100015521","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["K08DK124684,U01DK085527,R01DK115728,R01DK126070,P30DK072517"],"award-info":[{"award-number":["K08DK124684,U01DK085527,R01DK115728,R01DK126070,P30DK072517"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["SELLER19GE0,SELLER20-KB,SELLERS16L0,CIL21G0"],"award-info":[{"award-number":["SELLER19GE0,SELLER20-KB,SELLERS16L0,CIL21G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005492","name":"Stanford University","doi-asserted-by":"crossref","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/100005492","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sellers Research and Clinical Development, LLC","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,22]]},"abstract":"<jats:p>\n                    Duodenal bicarbonate secretion is critical to epithelial protection, as well as nutrient digestion and absorption, and is impaired in cystic fibrosis (CF). We examined if linaclotide, typically used to treat constipation, may also stimulate duodenal bicarbonate secretion. Bicarbonate secretion was measured in vivo and in vitro using mouse and human duodenum (biopsies and enteroids). Ion transporter localization was identified with confocal microscopy, and de novo analysis of human duodenal single-cell RNA sequencing (scRNA-Seq) data sets was performed. Linaclotide increased bicarbonate secretion in mouse and human duodenum in the absence of cystic fibrosis transmembrane conductance regulator (CFTR) expression (\n                    <jats:italic>Cftr<\/jats:italic>\n                    -knockout mice) or function (CFTR\n                    <jats:sub>inh<\/jats:sub>\n                    -172). Na\n                    <jats:sup>+<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    exchanger 3 inhibition contributed to a portion of this response. Linaclotide-stimulated bicarbonate secretion was eliminated by down-regulated in adenoma (DRA,\n                    <jats:italic>SLC26A3<\/jats:italic>\n                    ) inhibition during loss of CFTR activity. ScRNA-Seq identified that 70% of villus cells expressed\n                    <jats:italic>SLC26A3<\/jats:italic>\n                    , but not\n                    <jats:italic>CFTR<\/jats:italic>\n                    , mRNA. Loss of CFTR activity and linaclotide increased apical brush border expression of DRA in non-CF and CF differentiated enteroids. These data provide further insights into the action of linaclotide and how DRA may compensate for loss of CFTR in regulating luminal pH. Linaclotide may be a useful therapy for CF individuals with impaired bicarbonate secretion.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.172364","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T12:00:44Z","timestamp":1718280044000},"source":"Crossref","is-referenced-by-count":6,"title":["DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function"],"prefix":"10.1172","volume":"9","author":[{"given":"Jessica B.","family":"Sarthi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie M.","family":"Trumbull","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayda M.","family":"Abazari","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-8430","authenticated-orcid":true,"given":"Vincent","family":"van Unen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology, Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua E.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology, Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Gammons","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc O.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-0199","authenticated-orcid":true,"given":"Onur","family":"Cil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin J.","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology, Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M.","family":"Sellers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition; and"},{"name":"Sellers Research and Clinical Development, LLC, Newark, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01296029"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120562"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.10.001"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.09.019"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13299"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00261.2017"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00386.2004"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7540com"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15323"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93686"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70358-1"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216112"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1083"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.01.002"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01192"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115149"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00338.2001"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.11.047"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2018.02.002"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108819"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03852-1"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.108"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.149930"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-018-1230-8"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2017.10"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00380"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00087.2003"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9247473"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.11.013"},{"issue":"suppl 4","key":"B30","first-page":"268","article-title":"Duodenal intracellular bicarbonate and the \u2018CF paradox\u2019","volume":"2","author":"Kaunitz","year":"2001","journal-title":"JOP"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.12.006"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.11.016"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.254854"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00225.2011"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121370"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1997.272.4.G872"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(98)90130-5"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.07.050"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/172364\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:41:55Z","timestamp":1779136915000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/172364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,13]]},"references-count":39,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7,22]]},"published-print":{"date-parts":[[2024,7,22]]}},"alternative-id":["10.1172\/jci.insight.172364"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.172364","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,13]]},"article-number":"e172364"}}