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Pediatr Res. 2017 May;81(5):795-805. doi: 10.1038/pr.2017.21. Epub 2017 Jan 31.

Caffeine administration modulates TGF-β signaling but does not attenuate blunted alveolarization in a hyperoxia-based mouse model of bronchopulmonary dysplasia.

Author information

1
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
2
Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen-University of Applied Sciences, Giessen, Germany.
3
Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
4
Department of Forensic and Clinical Toxicology, Labor Krone, Bad Salzuflen, Germany.
5
Faculty of Biology and Chemistry, Justus Liebig University, Giessen, Germany.

Abstract

BACKGROUND:

Caffeine is widely used to manage apnea of prematurity, and reduces the incidence of bronchopulmonary dysplasia (BPD). Deregulated transforming growth factor (TGF)-β signaling underlies arrested postnatal lung maturation in BPD. It is unclear whether caffeine impacts TGF-β signaling or postnatal lung development in affected lungs.

METHODS:

The impact of caffeine on TGF-β signaling in primary mouse lung fibroblasts and alveolar epithelial type II cells was assessed in vitro. The effects of caffeine administration (25 mg/kg/d for the first 14 d of postnatal life) on aberrant lung development and TGF-β signaling in vivo was assessed in a hyperoxia (85% O2)-based model of BPD in C57BL/6 mice.

RESULTS:

Caffeine downregulated expression of type I and type III TGF-β receptors, and Smad2; and potentiated TGF-β signaling in vitro. In vivo, caffeine administration normalized body mass under hyperoxic conditions, and normalized Smad2 phosphorylation detected in lung homogenates; however, caffeine administration neither improved nor worsened lung structure in hyperoxia-exposed mice, in which postnatal lung maturation was blunted.

CONCLUSION:

Caffeine modulated TGF-β signaling in vitro and in vivo. Caffeine administration was well-tolerated by newborn mice, but did not influence the course of blunted postnatal lung maturation in a hyperoxia-based experimental mouse model of BPD.

PMID:
28141790
DOI:
10.1038/pr.2017.21
[Indexed for MEDLINE]

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