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Preterm lung exhibits distinct spatiotemporal proteome expression at initiation of lung Injury

Citation

Pereira-Fantini, PM and Pang, B and Byars, SG and Oakley, RB and Perkins, EJ and Dargaville, PA and Davis, PG and Nie, S and Williamson, NA and Ignjatovic, V and Tingay, DG, Preterm lung exhibits distinct spatiotemporal proteome expression at initiation of lung Injury, American Journal of Respiratory Cell and Molecular Biology ISSN 1535-4989 (2019) [Refereed Article]

DOI: doi:10.1165/rcmb.2019-0084OC

Abstract

Objectives: To characterize time-dependent and regionally-specific injury patterns associated with early ventilation of the preterm lung using a mass-spectrometry based proteomic approach.

Methods: Preterm lambs delivered at gestational age 124-127d were randomized to receive 15-min (n=7) or 90-min (n=10) of mechanical ventilation at standardized settings (positive end-expiratory pressure 8 cmH2O, tidal volume 6-8 mL/kg) and were compared with unventilated control lambs (n=7). At study completion, lung tissue was taken from standardized gravity-dependent and non-dependent regions, and assessed for lung injury via histology, qPCR and by proteomic analysis via Orbitrap-mass spectrometry. Ingenuity Pathway Analysis Software was used to identify temporal and region-specific enrichments in pathways and functions.

Measurements and Main Results: Apoptotic cell numbers were 9-fold higher in non-dependent lung at 15- and 90-minutes compared to controls, whilst proliferative cells were increased 4-fold in the dependent lung at 90-minutes. The relative gene expression of lung injury markers was increased at 90-minutes in non-dependent lung (p<0.05) and unchanged in dependent lung. Within the proteome the number of differentially expressed proteins was 4-fold higher in the non-dependent lung than the dependent lung. The number of differential proteins increasing over time in both lung regions. 95% of enriched canonical pathways and 94% of enriched cellular and molecular functions were identified only in non-dependent lung tissue from the 90-min ventilation group.

Conclusions: Complex injury pathways are initiated within the preterm lung after 15 minutes of ventilation and amplified by continuing ventilation. Injury development is region-specific with greater alterations within the proteome of non-dependent lung.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Paediatrics and Reproductive Medicine
Research Field:Paediatrics
Objective Division:Health
Objective Group:Specific Population Health (excl. Indigenous Health)
Objective Field:Child Health
UTAS Author:Dargaville, PA (Professor Peter Dargaville)
ID Code:133800
Year Published:2019
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-07-10
Last Modified:2019-07-10
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