Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

Ri Kim So, Sun Lee Kyung, Ju Park Seoung, Hoon Min Kyung, Young Lee Ka, Hun Choe Yeong, Hyun Hong Sang, Young Koh Gou, Chul Lee Yong

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)- inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-α, IL-1β, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1α (HIF-1α) and NF-κB in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H 2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1α and NF-κB and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.

Original languageEnglish
Pages (from-to)320-331
Number of pages12
JournalExperimental and Molecular Medicine
Volume40
Issue number3
DOIs
Publication statusPublished - 2008 Jun 30

Keywords

  • Angiopoietin-1
  • COMP-Ang1 fusion protein
  • Capillary permeability
  • Hydrogen peroxide
  • Lung
  • Pneumonia
  • Reactive oxygen species
  • Vascular endothelial growth factor A

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury'. Together they form a unique fingerprint.

  • Cite this

    So, R. K., Kyung, S. L., Seoung, J. P., Kyung, H. M., Ka, Y. L., Yeong, H. C., Sang, H. H., Gou, Y. K., & Yong, C. L. (2008). Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury. Experimental and Molecular Medicine, 40(3), 320-331. https://doi.org/10.3858/emm.2008.40.3.320