Dual oxidase 2 in lung epithelia is essential for hyperoxia-induced acute lung injury in mice

Min Ji Kim, Jae Chan Ryu, Younghee Kwon, Suhee Lee, Yun Soo Bae, Joo Heon Yoon, Ji Hwan Ryu

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Aims: Acute lung injury (ALI) induced by excessive hyperoxia has been employed as a model of oxidative stress imitating acute respiratory distress syndrome. Under hyperoxic conditions, overloading quantities of reactive oxygen species (ROS) are generated in both lung epithelial and endothelial cells, leading to ALI. Some NADPH oxidase (NOX) family enzymes are responsible for hyperoxia-induced ROS generation in lung epithelial and endothelial cells. However, the molecular mechanisms of ROS production in type II alveolar epithelial cells (AECs) and ALI induced by hyperoxia are poorly understood.

Results: In this study, we show that dual oxidase 2 (DUOX2) is a key NOX enzyme that affects hyperoxia-induced ROS production, particularly in type II AECs, leading to lung injury. In DUOX2 mutant mice (DUOX2thyd/thyd) or mice in which DUOX2 expression is knocked down in the lungs, hyperoxia-induced ALI was significantly lower than in wild-type (WT) mice. DUOX2 was mainly expressed in type II AECs, but not endothelial cells, and hyperoxia-induced ROS production was markedly reduced in primary type II AECs isolated from DUOX2thyd/thyd mice. Furthermore, DUOX2-generated ROS are responsible for caspase-mediated cell death, inducing ERK and JNK phophorylation in type II AECs.

Innovation: To date, no role for DUOX2 has been defined in hyperoxia-mediated ALI despite it being a NOX homologue and major ROS source in lung epithelium.

Conclusion: Here, we present the novel finding that DUOX2-generated ROS induce AEC death, leading to hyperoxia-induced lung injury.

Original languageEnglish
Pages (from-to)1803-1818
Number of pages16
JournalAntioxidants and Redox Signaling
Volume21
Issue number13
DOIs
StatePublished - 1 Nov 2014

Fingerprint

Dive into the research topics of 'Dual oxidase 2 in lung epithelia is essential for hyperoxia-induced acute lung injury in mice'. Together they form a unique fingerprint.

Cite this