Dataset Information

Age-related differences in structure and function of nasal epithelial cultures from healthy children and elderly people

ABSTRACT: The nasal epithelium represents the first line of defense against inhaled pathogens, allergens, and irritants and plays a key role in the pathogenesis of a spectrum of acute and chronic airways diseases. Despite age-dependent clinical phenotypes triggered by these noxious stimuli, little is known about how ageing affects the structure and function of the airway epithelium that is crucial for lung homeostasis and host defense. The aim of this study was therefore to determine age-related differences in structural and functional properties of primary nasal epithelial cultures from healthy children and non-smoking elderly people. To achieve this goal, highly differentiated nasal epithelial cultures were established from nasal brushes at air-liquid-interface and used to study epithelial cell type composition, mucin (MUC5AC and MUC5B) expression and ion transport properties. Further, we determined age-dependent molecular signatures using global proteomic analysis. We found lower numeric densities of ciliated cells and higher levels of MUC5AC expression in cultures from children vs. elderly people. Bioelectric studies showed no differences in basal ion transport properties, ENaC-mediated sodium absorption or CFTR-mediated chloride transport, but detected decreased calcium-activated TMEM16A-mediated chloride secretory responses in cultures from children vs. elderly people. Proteome analysis identified distinct age-dependent molecular signatures associated with ciliation and mucin biosynthesis, as well as other pathways implicated in ageing. Our data identified intrinsic, age-related differences in structure and function of the nasal epithelium and provide a basis for further studies on the role of these findings in age-dependent airways disease phenotypes observed with a spectrum of respiratory infections and other noxious stimuli.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Michael Mülleder

LAB HEAD: Marcus Mall

PROVIDER: PXD030130 | Pride | 2022-02-28

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20210909_PRO2_LS_02_50-0060_S25_0.678_D1_GD1_1_767.d.zip	Other
	20210909_PRO2_LS_03_50-0060_S16_0.727_B8_GB8_1_769.d.zip	Other
	20210909_PRO2_LS_04_50-0060_S24_0.563_C8_GC8_1_771.d.zip	Other
	20210909_PRO2_LS_05_50-0060_S14_0.482_B6_GB6_1_773.d.zip	Other
	20210909_PRO2_LS_06_50-0060_S19_0.563_C3_GC3_1_775.d.zip	Other

Items per page:

1 - 5 of 30

Similar Datasets

Project description:Propylene glycol (PG) is a common carrier in e-vapor formulations and its properties have been extensively studied. In this 13-week subchronic nose-only inhalation study, Sprague Dawley rats were exposed to filtered air (sham control group), propylene glycol/water (PG/W; 90:10) or a propylene glycol/vegetable glycerin/water (PG/VG/W; 50:40:10) reference. The reference containing vegetable glycerin group was added at the high dose to observe any changes that might be associated with a carrier more in line with e-vapor products. The objectives of this study were to increase the PG exposure above the concentrations tested by Suber et al. and use a systems toxicology analysis of lung tissue to further our understanding of molecular events after PG exposures (Suber et al. 1989). Macroscopic examinations at necropsy as well as terminal organ weights revealed no observations that were associated with exposure to PG/W or reference. Food consumption and body weights were unaffected by PG/W or reference when compared to the sham. No exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or BALF cytology and clinical chemistry. Although clinical observations of dried red material around the nose in the high dose PG/W group were reported, histopathology of the nasal cavity showed no nasal hemorrhaging. There were non-adverse PG/W and reference related findings of minimal mucus cell hyperplasia noted in nasal cavity section II. These findings were considered non-adverse as they were also found to a lesser extent in the filtered air controls. No other exposure-related findings were noted in the primary or recovery necropsies. A systems toxicology analysis on lung tissue showed no statistically-significant differentially expressed transcripts or proteins compared to the sham group. The endpoints measured from the PG/W high dose group did not differ significantly from those in the more common carrier PG/VG/W. Accordingly, the highest PG exposure (5 mg/L, 6 hrs/day) was regarded as the no observed adverse effect concentration (NOAEC), corresponding to a PG delivered dose of 1,152 mg/kg/day in rats.

Dataset Information

Age-related differences in structure and function of nasal epithelial cultures from healthy children and elderly people

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets