{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T20:23:06Z","timestamp":1792959786220,"version":"4.5.0"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"crossref","award":["FFC#1-2019"],"award-info":[{"award-number":["FFC#1-2019"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"crossref","award":["FFC#9-2019"],"award-info":[{"award-number":["FFC#9-2019"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"crossref","award":["TFCF"],"award-info":[{"award-number":["TFCF"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,20]]},"abstract":"<jats:p>In recent years, a number of drugs have been approved for the treatment of cystic fibrosis (CF). Among them, newly released Trikafta, a combination of 3 drugs (VX-661\/VX-445\/VX-770), holds great promise to radically improve the quality of life for a large portion of patients with CF carrying 1 copy of F508del, the most frequent CF transmembrane conductance regulator (CFTR) mutation. Currently available disease-modifying CF drugs work by rescuing the function of the mutated CFTR anion channel. Recent research has shown that membrane lipids, and the cell lipidome in general, play a significant role in the mechanism of CFTR-defective trafficking and, on the other hand, its rescue. In this paper, by using untargeted lipidomics on CFBE41o- cells, we identified distinctive changes in the bronchial epithelial cell lipidome associated with treatment with Trikafta and other CF drugs. Particularly interesting was the reduction of levels of ceramide, a known molecular player in the induction of apoptosis, which appeared to be associated with a decrease in the susceptibility of cells to undergo apoptosis. This evidence could account for additional beneficial roles of the triple combination of drugs on CF phenotypes.<\/jats:p>","DOI":"10.1172\/jci.insight.138722","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T12:01:41Z","timestamp":1594900901000},"source":"Crossref","is-referenced-by-count":32,"title":["Distinctive lipid signatures of bronchial epithelial cells associated with cystic fibrosis drugs, including Trikafta"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-4753","authenticated-orcid":true,"given":"Nara","family":"Liessi","sequence":"first","affiliation":[{"name":"Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Pesce","sequence":"additional","affiliation":[{"name":"L\u2019Unit\u00e0 Operativa Complessa (UOC) Genetica Medica, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Giannina Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Braccia","sequence":"additional","affiliation":[{"name":"D3 PharmaChemistry, Istituto Italiano di Tecnologia, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sine Mandrup","family":"Bertozzi","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5291-0837","authenticated-orcid":true,"given":"Alessandro","family":"Giraudo","sequence":"additional","affiliation":[{"name":"D3 PharmaChemistry, Istituto Italiano di Tecnologia, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2496-2701","authenticated-orcid":true,"given":"Tiziano","family":"Bandiera","sequence":"additional","affiliation":[{"name":"D3 PharmaChemistry, Istituto Italiano di Tecnologia, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5161-1720","authenticated-orcid":true,"given":"Nicoletta","family":"Pedemonte","sequence":"additional","affiliation":[{"name":"L\u2019Unit\u00e0 Operativa Complessa (UOC) Genetica Medica, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Giannina Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3766-8755","authenticated-orcid":true,"given":"Andrea","family":"Armirotti","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.598649"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201812143"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2016.11.013"},{"issue":"9","key":"B4","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/j.bbamcr.2016.06.005","article-title":"The phospholipid flippase ATP8B1 mediates apical localization of the cystic fibrosis transmembrane regulator","volume":"1863","author":"van der Mark","year":"2016","journal-title":"Biochim Biophys Acta"},{"issue":"8","key":"B5","doi-asserted-by":"crossref","DOI":"10.3390\/cells8080804","article-title":"Cholesterol interaction directly enhances intrinsic activity of the cystic fibrosis transmembrane conductance regulator (CFTR)","volume":"8","author":"Chin","year":"2019","journal-title":"Cells"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201700709"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63639-3.00020-7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7704-8_17"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2174\/1874467208666150817111419"},{"issue":"7","key":"B10","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20071623","article-title":"Kidney lipidomics by mass spectrometry imaging: a focus on the glomerulus","volume":"20","author":"Abbas","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13782"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2018.10.004"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-120-8_14"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s10337-014-2787-5"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007735"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P013722"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2019.04.012"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125326"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130313"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00298.2016"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008889"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008680"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1807120"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay9669"},{"key":"B25"},{"issue":"Suppl 1","key":"B26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11306-011-0330-3","article-title":"Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies","volume":"8","author":"Szyma\u0144ska","year":"2012","journal-title":"Metabolomics"},{"issue":"Web Server issue","key":"B27","doi-asserted-by":"crossref","first-page":"W606","DOI":"10.1093\/nar\/gkm324","article-title":"LIPID MAPS online tools for lipid research","volume":"35","author":"Fahy","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.112177"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3109\/09687688.2015.1066894"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/la9026283"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75223-5"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(94)90263-1"},{"issue":"2","key":"B33","first-page":"233","article-title":"Lipid composition of airway secretions from patients with asthma and patients with cystic fibrosis","volume":"115","author":"Sahu","year":"1977","journal-title":"Am Rev Respir Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28929"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2014.01.004"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2018.08.003"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1511-4_13"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.04.015"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-015-8585-6"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.22.4.3376"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.25.6.4321"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00408.2010"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0422OC"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.08.025"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16147"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/81.3.686"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00422-7"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021715"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400034"},{"issue":"9 Pt B","key":"B50","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.bbamem.2017.05.017","article-title":"Membrane-lipid therapy: A historical perspective of membrane-targeted therapies - From lipid bilayer structure to the pathophysiological regulation of cells","volume":"1859","author":"Escrib\u00e1","year":"2017","journal-title":"Biochim Biophys Acta Biomembr"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.131"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0438003100"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D700041-JLR200"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1021\/ac500317c"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/metabo3030701"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky310"},{"key":"B57","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2164-7-142","article-title":"Centering, scaling, and transformations: improving the biological information content of metabolomics data","volume":"7","author":"van den Berg","year":"2006","journal-title":"BMC Genomics"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2017\/29763.10812"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1089"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-017-2006-0"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2014.04.017"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s13361-016-1469-y"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/2047-217X-2-13"},{"key":"B64","doi-asserted-by":"crossref","first-page":"14.13.1","DOI":"10.1002\/0471250953.bi1413s53","article-title":"MetaboLights: an open-access database repository for metabolomics data","volume":"53","author":"Kale","year":"2016","journal-title":"Curr Protoc Bioinformatics"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/138722\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:54:55Z","timestamp":1779152095000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/138722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":64,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2020,8,20]]},"published-print":{"date-parts":[[2020,8,20]]}},"alternative-id":["10.1172\/jci.insight.138722"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.138722","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,20]]},"article-number":"e138722"}}