{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:05:58Z","timestamp":1779973558222,"version":"3.53.1"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis is a multi-organ disease in which pancreatic involvement occurs early and contributes significantly to disease progression. Despite this, most mechanistic and pharmacological studies of CFTR have been conducted in airway epithelia, while pancreatic duct models remain relatively poorly represented. In this study, we establish CAPAN-1 cells as a reproducible in vitro model of pancreatic duct epithelium and assess wild-type CFTR function under basal and inflammatory conditions. Cells were cultured as polarized monolayers and analysed for transepithelial conductance, ion transport, luminal fluid pH regulation, and microviscosity. CFTR activity was stimulated with forskolin and further modulated using the potentiator ivacaftor (VX770) and the correctors tezacaftor (VX661) and elexacaftor (VX445), while specificity was confirmed with the CFTR inhibitor PPQ102. Inflammation was induced by lipopolysaccharide (LPS). CAPAN-1 cells formed a functional epithelium. CFTR activation increased epithelial conductance, promoted apical surface fluid alkalinization, and reduced apical surface fluid microviscosity, while PPQ102 consistently inhibited these effects. CFTR modulators enhanced functional responses in the presence of forskolin, although with moderate magnitude, consistent with wild-type CFTR expression. LPS exposure altered epithelial properties, increasing baseline conductance and impairing pH regulation, and induced secretion of pro-inflammatory cytokines. Notably, inflammatory stimulation did not abolish CFTR modulator responses, although it modified some downstream epithelial outputs. These findings identify CAPAN-1 cells as a physiologically relevant model for investigating CFTR function in the pancreatic duct environment and show that CFTR modulator responses are maintained, although functionally reshaped, under inflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms27114868","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"4868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Rescue of CFTR-Dependent Transport in a Pancreatic Ductal Epithelial Cell Model: The Impact of Pharmacological Modulation and Inflammation"],"prefix":"10.3390","volume":"27","author":[{"given":"Alessandra","family":"Ludovico","sequence":"first","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini, 6, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3233-8396","authenticated-orcid":false,"given":"Martina","family":"Battistini","sequence":"additional","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini, 6, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-2468","authenticated-orcid":false,"given":"Debora","family":"Baroni","sequence":"additional","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini, 6, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/humu.10041","article-title":"Cystic fibrosis: A worldwide analysis of CFTR mutations, correlation with incidence data and application to screening","volume":"19","author":"Bobadilla","year":"2002","journal-title":"Hum. 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