Role of mitochondrial hydrogen peroxide induced by intermittent hypoxia in airway epithelial wound repair in vitro

Satoshi Hamada, Atsuyasu Sato, Mariko Hara-Chikuma, Hiroki Satooka, Koichi Hasegawa, Kazuya Tanimura, Kiminobu Tanizawa, Morito Inouchi, Tomohiro Handa, Toru Oga, Shigeo Muro, Michiaki Mishima, Kazuo Chin

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


The airway epithelium acts as a frontline barrier against various environmental insults and its repair process after airway injury is critical for the lung homeostasis restoration. Recently, the role of intracellular reactive oxygen species (ROS) as transcription-independent damage signaling has been highlighted in the wound repair process. Both conditions of continuous hypoxia and intermittent hypoxia (IH) induce ROS. Although IH is important in clinical settings, the roles of IH-induced ROS in the airway repair process have not been investigated. In this study, we firstly showed that IH induced mitochondrial hydrogen peroxide (H2O2) production and significantly decreased bronchial epithelial cell migration, prevented by catalase treatment in a wound scratch assay. RhoA activity was higher during repair process in the IH condition compared to in the normoxic condition, resulting in the cellular morphological changes shown by immunofluorescence staining: round cells, reduced central stress fiber numbers, pronounced cortical actin filament distributions, and punctate focal adhesions. These phenotypes were replicated by exogenous H2O2 treatment under the normoxic condition. Our findings confirmed the transcription-independent role of IH-induced intracellular ROS in the bronchial epithelial cell repair process and might have significant implications for impaired bronchial epithelial cell regeneration.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalExperimental Cell Research
Issue number1
Publication statusPublished - 2016 May 15
Externally publishedYes


  • Actin cytoskeleton
  • Intermittent hypoxia
  • Reactive oxygen species
  • RhoA
  • Transcription-independent manner
  • Wound repair

ASJC Scopus subject areas

  • Cell Biology


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