Abstract
Bronchopulmonary dysplasia (BPD) is a serious pulmonary disease which occurs in preterm infants. Mortality remains high due to a lack of effective treatment, despite significant progress in neonatal resuscitation. In BPD, a persistently high level of canonical WNT/β-catenin pathway activity at the canalicular stage disturbs the pulmonary maturation at the saccular and alveolar stages. The excessive thickness of the alveolar wall impairs the normal diffusion of oxygen and carbon dioxide, leading to hypoxia. Transforming growth factor (TGF-β) up-regulates canonical WNT signaling and inhibits the peroxysome proliferator activated receptor gamma (PPARγ). This profile is observed in BPD, especially in animal models. Following a premature birth, hypoxia activates the canonical WNT/TGF-β axis at the expense of PPARγ. This gives rise to the differentiation of fibroblasts into myofibroblasts, which can lead to pulmonary fibrosis that impairs the respiratory function after birth, during childhood and even adulthood. Potential therapeutic treatment could target the inhibition of the canonical WNT/TGF-β pathway and the stimulation of PPARγ activity, in particular by the administration of nebulized PPARγ agonists.
Highlights
Bronchopulmonary dysplasia (BPD) is a serious pulmonary disease occurring in preterm infants [1]
Several cascades are implied in lung organogenesis, such as bone-morphogenic proteins (BMPs), fibroblast growth factors (FGFs), sonic hedgehog (SHH), and the WNT family [30,31,32,33]
Significant prematurity predisposes to general hypoxia, in the pulmonary tissue. Both hypoxia and hyperoxia promote upregulation of the canonical WNT/βcatenin system and TGF-β and downregulation of PPARγ. This stops lung maturation and gives rise to the transdifferentiation of lipofibroblasts into myofibroblasts, which may lead to pulmonary fibrosis and severe pulmonary sequelae
Summary
Bronchopulmonary dysplasia (BPD) is a serious pulmonary disease occurring in preterm infants [1]. In BPD, PPARγ has been shown to be downregulated in several animal models, while the canonical WNT/β-catenin pathway has been upregulated. The absence of a decrease in the WNT/β-catenin signaling during the canalicular stage of pulmonary development, partly related to inflammatory processes, a hallmark of BPD, will seriously affect normal development in the subsequent saccular and alveolar stages [7]. This is responsible for the respiratory distress at birth and the often severe and irreversible sequelae observed in childhood and adulthood. We review the respective roles in BPD of both the canonical WNT pathway and PPARγ, which are determined by TGFβ signaling, and discuss their possible implications for the therapeutic treatment of BPD
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
