Language
English
Publication Date
1-8-2024
Journal
Antioxidants
DOI
10.3390/antiox13010078
PMID
38247502
PMCID
PMC10812697
PubMedCentral® Posted Date
1-8-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Interrupted lung angiogenesis is a hallmark of bronchopulmonary dysplasia (BPD); however, druggable targets that can rescue this phenotype remain elusive. Thus, our investigation focused on amphiregulin (Areg), a growth factor that mediates cellular proliferation, differentiation, migration, survival, and repair. While Areg promotes lung branching morphogenesis, its effect on endothelial cell (EC) homeostasis in developing lungs is understudied. Therefore, we hypothesized that Areg promotes the proangiogenic ability of the ECs in developing murine lungs exposed to hyperoxia. Lung tissues were harvested from neonatal mice exposed to normoxia or hyperoxia to determine Areg expression. Next, we performed genetic loss-of-function and pharmacological gain-of-function studies in normoxia- and hyperoxia-exposed fetal murine lung ECs. Hyperoxia increased Areg mRNA levels and Areg+ cells in whole lungs. While Areg expression was increased in lung ECs exposed to hyperoxia, the expression of its signaling receptor, epidermal growth factor receptor, was decreased, indicating that hyperoxia reduces Areg signaling in lung ECs. Areg deficiency potentiated hyperoxia-mediated anti-angiogenic effects. In contrast, Areg treatment increased extracellular signal-regulated kinase activation and exerted proangiogenic effects. In conclusion, Areg promotes EC tubule formation in developing murine lungs exposed to hyperoxia.
Keywords
angiogenesis, amphiregulin, fetal murine lung endothelial cells, hyperoxia, bronchopulmonary dysplasia
Published Open-Access
yes
Recommended Citation
Thapa, Shyam; Shankar, Nithyapriya; Shrestha, Amrit Kumar; et al., "Amphiregulin Exerts Proangiogenic Effects in Developing Murine Lungs" (2024). Faculty and Staff Publications. 5956.
https://digitalcommons.library.tmc.edu/baylor_docs/5956