Faculty Collaboration Database

Hyperoxia-induced airflow restriction and Renin-Angiotensin System expression in a bronchopulmonary dysplasia mouse model. Physiol Rep 2024 Jan;12(1):e15895

Date

01/02/2024

Pubmed ID

38163662

Pubmed Central ID

PMC10758334

DOI

10.14814/phy2.15895

Scopus ID

2-s2.0-85181507753 (requires institutional sign-in at Scopus site)

Abstract

Mechanisms underlying hyperoxia-induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin-Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro-developmental pathway consisting of angiotensin converting enzyme-2 (ACE2) and angiotensin II receptor type 2 (AT2), and a pro-fibrotic pathway mediated by angiotensin II receptor type 1 (AT1). We investigated associations between neonatal hyperoxia, airflow restriction, and RAS activity in a BPD mouse model. C57 mouse pups were randomized to normoxic (FiO₂  = 0.21) or hyperoxic (FiO₂  = 0.75) conditions for 15 days (P1-P15). At P15, P20, and P30, we measured airflow restriction using plethysmography and ACE2, AT1, and AT2 mRNA and protein expression via polymerase chain reaction and Western Blot. Hyperoxia increased airflow restriction P15 and P20, decreased ACE2 and AT2 mRNA, decreased AT2 protein, and increased AT1 protein expression. ACE2 mRNA and protein remained suppressed at P20. By P30, airflow restriction and RAS expression did not differ between groups. Hyperoxia caused high airflow restriction, increased pulmonary expression of the pro-fibrotic RAS pathway, and decreased expression of the pro-developmental in our BPD mouse model. These associated findings may point to a causal role for RAS in hyperoxia-induced airflow restriction.

Author List

Dowell J, Bice Z, Yan K, Konduri GG

Authors

Jasmine C. Dowell MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Bronchopulmonary Dysplasia
Disease Models, Animal
Fibrosis
Hyperoxia
Lung
Mice
RNA, Messenger
Renin-Angiotensin System