{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:28Z","timestamp":1787028568920,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Institute for Risk Assessment","award":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"],"award-info":[{"award-number":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"]}]},{"name":"Federal Institute for Risk Assessment","award":["GRK2338"],"award-info":[{"award-number":["GRK2338"]}]},{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) within the Research Training Group","award":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"],"award-info":[{"award-number":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"]}]},{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) within the Research Training Group","award":["GRK2338"],"award-info":[{"award-number":["GRK2338"]}]},{"name":"Helmholtz Association","award":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"],"award-info":[{"award-number":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"]}]},{"name":"Helmholtz Association","award":["GRK2338"],"award-info":[{"award-number":["GRK2338"]}]},{"name":"German Center for Lung Research","award":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"],"award-info":[{"award-number":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"]}]},{"name":"German Center for Lung Research","award":["GRK2338"],"award-info":[{"award-number":["GRK2338"]}]},{"name":"CPC Research School \u201cLung Biology and Disease\u201d","award":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"],"award-info":[{"award-number":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"]}]},{"name":"CPC Research School \u201cLung Biology and Disease\u201d","award":["GRK2338"],"award-info":[{"award-number":["GRK2338"]}]},{"name":"University of Colorado School of Medicine","award":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"],"award-info":[{"award-number":["Bundesinstitut f\u00fcr Risikobewertung, BfR, #1328-570"]}]},{"name":"University of Colorado School of Medicine","award":["GRK2338"],"award-info":[{"award-number":["GRK2338"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholesterol is an essential plasma membrane component, and altered cholesterol metabolism has been linked to cholesterol accumulation in the airways of COPD and cystic fibrosis patients. However, its role in airway epithelial differentiation is not well understood. Tandem mass spectrometry-based proteomic analysis of differentiating primary human bronchial epithelial cells (phBECs) revealed an overall inhibition of the cholesterol biosynthesis pathway. We hypothesized that excess cholesterol impairs the differentiation of phBECs into a fully functional bronchial epithelium. PhBECs were differentiated in the presence of 80 \u00b5M cholesterol for 21 days, the main airway cell type populations monitored using qRT-PCR and immunofluorescent stainings, and epithelial barrier integrity was analyzed via transepithelial electrical resistance measurements. Chronic cholesterol exposure led to a significant increase in CC10+ secretory cells at the expense of ciliated cells. Pathway enrichment analysis suggested the tumor protein p53 as a master regulator of genes during normal differentiation of phBECs. Chronic cholesterol exposure drastically impaired the nuclear translocation of p53. Our findings suggest that this inhibition underlies the cholesterol-induced expansion of CC10+ secretory cell populations at the expense of ciliated cells. In conclusion, we identify cholesterol as an important regulator of normal bronchial epithelial cell differentiation through inhibition of p53 nuclear translocation.<\/jats:p>","DOI":"10.3390\/ijms26178324","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"8324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation"],"prefix":"10.3390","volume":"26","author":[{"given":"Ashesh","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Institute of Lung Health and Immunity and Comprehensive Pneumology Center with the CPC-M bioArchive, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen and Helmholtz Zentrum M\u00fcnchen, Member of the German Center for Lung Research (DZL), 85764 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Giraldo-Arias","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity and Comprehensive Pneumology Center with the CPC-M bioArchive, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen and Helmholtz Zentrum M\u00fcnchen, Member of the German Center for Lung Research (DZL), 85764 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-4083","authenticated-orcid":false,"given":"Juliane","family":"Merl-Pham","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Dick","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity and Comprehensive Pneumology Center with the CPC-M bioArchive, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Marchi","sequence":"additional","affiliation":[{"name":"Core Facility Statistical Consulting, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany"},{"name":"Faculty of Business Administration and Economics, Bielefeld University, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9429-9925","authenticated-orcid":false,"given":"Ronan","family":"Le Gleut","sequence":"additional","affiliation":[{"name":"Core Facility Statistical Consulting, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"Hatz","sequence":"additional","affiliation":[{"name":"Thoraxchirurgisches Zentrum, Klinik f\u00fcr Allgemeine-, Viszeral-, Transplantations-, Gef\u00e4\u00df- und Thoraxchirurgie, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 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