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

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Pereira-Fantini, PM, Pang, B, Byars, SG, Oakley, RB, Perkins, EJ, Dargaville, PA, Davis, PG, Nie, S, Williamson, NA, Ignjatovic, V and Tingay, DG 2019 , 'Preterm lung exhibits distinct spatiotemporal proteome expression at initiation of lung Injury' , American Journal of Respiratory Cell and Molecular Biology, vol. 61, no. 5 , pp. 631-642 , doi: 10.1165/rcmb.2019-0084OC.

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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 (pConclusions: 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 Type: Article
Authors/Creators: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
Journal or Publication Title: American Journal of Respiratory Cell and Molecular Biology
Publisher: American Thoracic Society
ISSN: 1535-4989
DOI / ID Number: 10.1165/rcmb.2019-0084OC
Copyright Information:

Copyright © 2019 by the American Thoracic Society

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