{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:12:05Z","timestamp":1779199925908,"version":"3.51.4"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"19","funder":[{"name":"NIH","award":["DK080834"],"award-info":[{"award-number":["DK080834"]}]},{"name":"NIH","award":["DK093045"],"award-info":[{"award-number":["DK093045"]}]},{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"crossref","award":["ARORA16F0"],"award-info":[{"award-number":["ARORA16F0"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"crossref","award":["NAREN 14XX0"],"award-info":[{"award-number":["NAREN 14XX0"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,5]]},"abstract":"<jats:p>\n                    Cystic fibrosis (CF) is a genetic disorder in which epithelium-generated fluid flow from the lung, intestine, and pancreas is impaired due to mutations disrupting CF transmembrane conductance regulator (CFTR) channel function. CF manifestations of the pancreas and lung are present in the vast majority of CF patients, and 15% of CF infants are born with obstructed gut or meconium ileus. However, constipation is a significantly underreported outcome of CF disease, affecting 47% of the CF patients, and management becomes critical in the wake of increasing life span of CF patients. In this study, we unraveled a potentially novel molecular role of a membrane-bound cyclic guanosine monophosphate\u2013synthesizing (cGMP-synthesizing) intestinal enzyme, guanylate cyclase 2C (GCC) that could be targeted to ameliorate CF-associated intestinal fluid deficit. We demonstrated that GCC agonism results in functional rescue of murine F508del\/F508del and R117H\/R117H\n                    <jats:italic>Cftr<\/jats:italic>\n                    and CFTR mutants in CF patient\u2013derived intestinal spheres. GCC coexpression and activation facilitated processing and ER exit of F508del CFTR and presented a potentially novel rescue modality in the intestine, similar to the CF corrector VX-809. Our findings identify GCC as a biological CFTR corrector and potentiator in the intestine.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.93686","type":"journal-article","created":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T11:00:45Z","timestamp":1507114845000},"source":"Crossref","is-referenced-by-count":21,"title":["Guanylate cyclase 2C agonism corrects CFTR mutants"],"prefix":"10.1172","volume":"2","author":[{"given":"Kavisha","family":"Arora","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-9499","authenticated-orcid":true,"given":"Yunjie","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyushik","family":"Mun","sequence":"additional","affiliation":[{"name":"Division 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USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline B.","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Synlogic, Cambridge, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Silos-Santiago","sequence":"additional","affiliation":[{"name":"Decibel Therapeutics, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Helmrath","sequence":"additional","affiliation":[{"name":"Department of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph J.","family":"Palermo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John 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