Receptor for advanced glycation end products expressed on alveolar epithelial cells is the main target for hyperoxia-induced lung injury

Chiharu Ota, Kota Ishizawa, Mitsuhiro Yamada, Yukiko Tando, Mei He, Toru Takahashi, Mutsuo Yamaya, Yasuhiko Yamamoto, Hiroshi Yamamoto, Shigeo Kure, Hiroshi Kubo

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Background: Receptor for advanced glycation end products (RAGE) is abundantly expressed on alveolar epithelial cells (AECs) and participates in innate immune responses such as apoptosis and inflammation. However, it is unclear whether RAGE-mediated apoptosis of AECs is associated with hyperoxia-induced lung injury. Methods: We used wild-type and RAGE-knockout C57BL6/J mice in this study. In addition, we developed bone marrow chimeric mouse models expressing RAGE on hematopoietic or non-hematopoietic cells, including lung parenchymal cells, and compared survival ratios and changes in the permeability of the alveolar-capillary barrier after hyperoxia exposure. Further, we prepared single cell suspensions of lung cells and evaluated the apoptosis of AECs or microvascular endothelial cells (MVECs) by using a combination of antibodies and JC-dye. We also examined whether RAGE inhibition decreased hyperoxia-induced apoptosis of human lung epithelial cells in vitro. Results: After hyperoxia exposure, mice expressing RAGE on lung cells showed lower survival rate and increased alveolar-capillary permeability than mice expressing RAGE on hematopoietic cells. RAGE-expressing AECs showed significantly higher apoptosis than RAGE-knockout AECs after in vivo hyperoxia exposure. The level of hyperoxia-induced apoptosis was not different in MVECs. However, RAGE-null lung epithelial cells showed lower apoptosis than RAGE-expressing cells in vitro. Conclusion: These results indicated that RAGE on AECs mainly contributed to hyperoxia-induced lung injury and alveolar-capillary barrier disruption.

Original languageEnglish
Pages (from-to)98-108
Number of pages11
JournalRespiratory Investigation
Issue number2
Publication statusPublished - 2016 Mar 1


  • Alveolar epithelial cells
  • Alveolar-capillary barrier integrity
  • Hyperoxia
  • Microvascular endothelial cells
  • Receptor for advanced glycation end products

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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