Language
English
Publication Date
3-2-2023
Journal
Antioxidants
DOI
10.3390/antiox12030620
PMID
36978868
PMCID
PMC10045755
PubMedCentral® Posted Date
3-2-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Inflammation causes bronchopulmonary dysplasia (BPD), a common lung disease of preterm infants. One reason this disease lacks specific therapies is the paucity of information on the mechanisms regulating inflammation in developing lungs. We address this gap by characterizing the lymphatic phenotype in an experimental BPD model because lymphatics are major regulators of immune homeostasis. We hypothesized that hyperoxia (HO), a major risk factor for experimental and human BPD, disrupts lymphatic endothelial homeostasis using neonatal mice and human dermal lymphatic endothelial cells (HDLECs). Exposure to 70% O2 for 24–72 h decreased the expression of prospero homeobox 1 (Prox1) and vascular endothelial growth factor c (Vegf-c) and increased the expression of heme oxygenase 1 and NAD(P)H dehydrogenase [quinone]1 in HDLECs, and reduced their tubule formation ability. Next, we determined Prox1 and Vegf-c mRNA levels on postnatal days (P) 7 and 14 in neonatal murine lungs. The mRNA levels of these genes increased from P7 to P14, and 70% O2 exposure for 14 d (HO) attenuated this physiological increase in pro-lymphatic factors. Further, HO exposure decreased VEGFR3+ and podoplanin+ lymphatic vessel density and lymphatic function in neonatal murine lungs. Collectively, our results validate the hypothesis that HO disrupts lymphatic endothelial homeostasis.
Keywords
lymphangiogenesis, lymphatic function, human dermal lymphatic endothelial cells, hyperoxia, bronchopulmonary dysplasia
Published Open-Access
yes
Recommended Citation
Shankar, Nithyapriya; Thapa, Shyam; Shrestha, Amrit Kumar; et al., "Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice" (2023). Faculty, Staff and Students Publications. 5957.
https://digitalcommons.library.tmc.edu/baylor_docs/5957