Dataset Information

Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Bronchial Epithelial Cell

SUBMITTER: Juliane Merl-Pham

LAB HEAD: Ashesh Chakraborty

PROVIDER: PXD063763 | Pride | 2025-09-22

REPOSITORIES: Pride

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			Action	DRS
	STC12609X002__ASK291_Mock_D1_92-166187.raw	Raw
	STC12609X003__ASK291_Mock_D7_92-166188.raw	Raw
	STC12609X004__ASK291_Mock_D14_92-166189.raw	Raw
	STC12609X005__ASK291_Mock_D21_92-166190.raw	Raw
	STC12609X006__ASK291_Mock_D28_92-166191.raw	Raw

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Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation.

Chakraborty Ashesh A Giraldo-Arias Juliana J Merl-Pham Juliane J Dick Elisabeth E Mastalerz Michal M Zöller Marie M Marchi Hannah H Le Gleut Ronan R Hatz Rudolf A RA Behr Jürgen J Hilgendorff Anne A Hauck Stefanie M SM Staab-Weijnitz Claudia A CA

International journal of molecular sciences 20250827 17

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 imp ...[more]

PMID: 40943244

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