Yi Jin, Bernadette Chen, Yusen Liu, Leif D. Nelin
Nationwide Children’s Hospital and Ohio State University.
United States
American Journal of Physiology Lung Cellular and Molecular Physiology
Am J Physiol Lung Cell Mol Physiol 2025;
DOI: 10.1152/ajplung.00202.2024
Abstract
Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in pediatrics. Neonatal mice placed in hyperoxia (85% oxygen, HYP) develop lung injury reminiscent of BPD. We tested the hypothesis that mice deficient in arginase-2 (Arg2KO) exposed to HYP would have attenuated lung inflammation and injury compared to similarly exposed wild-type mice. Arg2KO and C57BL/6 (WT) mice were placed in either room air (NORM) or HYP on postnatal day 0 (P0) and exposed for up to 14 days. RNAseq data on P1 and P14 showed that HYP differentially up-regulated genes particularly those related to development and inflammation between the two genotypes. Neonatal mice exposed to HYP had evidence of alveolar simplification at P7 and P14, which was slightly attenuated in Arg2KO mice. After 14 days in HYP mice were moved to NORM and methacholine challenge testing was performed at 6, 8, or 12 weeks of age. WT mice exposed to neonatal hyperoxia showed greater methacholine-induced respiratory system resistance (RRS) at 6 and 8 weeks of age compared to WT mice exposed to NORM. The methacholine-induced increase in RRS in Arg2KO mice exposed to neonatal hyperoxia was not different from normoxia exposed mice of either genotype. At 6, 8, and 12 weeks, alveolar simplification was evident in both WT and Arg2KO mice exposed to neonatal hyperoxia with no differences between genotypes. These data demonstrate that Arg2KO attenuated both the hyperoxia-induced lung inflammation at P1 and P14 and the airway hyperreactivity at 6 and 8 weeks of age.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Class I. Pulmonary Hypertension Associated with Inflammation
Animal Models of Pulmonary Vascular Disease and Therapy
Genetic Factors Associated with Pulmonary Vascular Disease
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes