Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice

Nithyapriya Shankar, Shyam Thapa, Amrit Kumar Shrestha, Poonam Sarkar, M. Waleed Gaber, Roberto Barrios, Binoy Shivanna

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number620
Issue number3
StatePublished - Mar 2 2023


  • bronchopulmonary dysplasia
  • human dermal lymphatic endothelial cells
  • hyperoxia
  • lymphangiogenesis
  • lymphatic function

ASJC Scopus subject areas

  • Food Science
  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice'. Together they form a unique fingerprint.

Cite this