PXD063763-1

PXD063763 is an original dataset announced via ProteomeXchange.

Title	Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation
Description	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 presence of 80 µM 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 led to a significant increase of CC10+ secretory cells at the expense of ciliated cells. Pathway enrichment analysis suggested 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.
HostingRepository	PRIDE
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-21_23:31:37.615.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juliane Merl-Pham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-08 06:10:32	ID requested
⏵ 1	2025-09-21 23:31:38	announced

Chakraborty A, Giraldo-Arias J, Merl-Pham J, Dick E, Mastalerz M, Z, ö, ller M, Marchi H, Le Gleut R, Hatz RA, Behr J, Hilgendorff A, Hauck SM, Staab-Weijnitz CA, Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation. Int J Mol Sci, 26(17):(2025) [pubmed]

10.3390/ijms26178324;

submitter keyword: Ingenuity Pathway Analysis, primary human bronchial epithelial cells,Cholesterol, p53

Ashesh Chakraborty
contact affiliation	Institute of Lung Health and Immunity, and Comprehensive Pneumology Center with the CPC-M bioArchive, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, Munich, Germany, Member of the German Center for Lung Research (DZL).
contact email	ashesh.chakraborty@helmholtz-munich.de
lab head
Juliane Merl-Pham
contact affiliation	Metabolomics and Proteomics Core, Helmholtz Munich
contact email	juliane.merl@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD063763

PRIDE project URI

• PRIDE
  1. PXD063763
     1. Label: PRIDE project
     2. Name: Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation