Journal article

Publication year: 2017

Pages: 795-805

Journal: Pediatric Research

Volume number: 81

Issue number: 5

ISSN: 0031-3998

eISSN: 1530-0447

Open access status: Bronze

DOI Link: https://doi.org/10.1038/pr.2017.21

Publisher: Springer Nature [academic journals on nature.com]

Abstract: 

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

METHODS: The impact of caffeine on TGF-beta 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-beta signaling in vivo was assessed in a hyperoxia (85% O-2)-based model of BPD in C57BU6 mice.

RESULTS: Caffeine downregulated expression of type I and type Ill TGF-beta receptors, and Smad2; and potentiated TGF-beta 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-beta 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.

Harvard Citation style: Rath, P., Nardiello, C., Solaligue, D., Agius, R., Mizikova, I., Huehn, S., et al. (2017) Caffeine administration modulates TGF-β signaling but does not attenuate blunted alveolarization in a hyperoxia-based mouse model of bronchopulmonary dysplasia, Pediatric Research, 81(5), pp. 795-805. https://doi.org/10.1038/pr.2017.21

APA Citation style: Rath, P., Nardiello, C., Solaligue, D., Agius, R., Mizikova, I., Huehn, S., Mayer, K., Vadasz, I., Herold, S., Runkel, F., Seeger, W., & Morty, R. (2017). Caffeine administration modulates TGF-β signaling but does not attenuate blunted alveolarization in a hyperoxia-based mouse model of bronchopulmonary dysplasia. Pediatric Research. 81(5), 795-805. https://doi.org/10.1038/pr.2017.21