Philipp Rath1,2, Claudio Nardiello1,3, David E Surate Solaligue1,3, Ronald Agius4, Ivana Mižíková1,3, Sebastian Hühn2, Konstantin Mayer3, István Vadász3, Susanne Herold3, Frank Runkel2,5, Werner Seeger1,3, Rory E Morty1,3. 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.
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.
Authors: Tuong-Van Hoang; Claudio Nardiello; David E Surate Solaligue; José Alberto Rodríguez-Castillo; Philipp Rath; Konstantin Mayer; István Vadász; Susanne Herold; Kathrin Ahlbrecht; Werner Seeger; Rory E Morty Journal: J Anat Date: 2018-01-09 Impact factor: 2.610
Authors: Huiling Li; Harry Karmouty-Quintana; Ning-Yuan Chen; Tingting Mills; Jose Molina; Michael R Blackburn; Jonathan Davies Journal: Pediatr Res Date: 2017-08-23 Impact factor: 3.756
Authors: Stefanie Obst; Josephine Herz; Miguel A Alejandre Alcazar; Stefanie Endesfelder; Marius A Möbius; Mario Rüdiger; Ursula Felderhoff-Müser; Ivo Bendix Journal: Oxid Med Cell Longev Date: 2022-02-24 Impact factor: 6.543