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

Ri Kim So, Sun Lee Kyung, Ju Park Seoung, Kyung-Hoon Min, 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
Externally publishedYes

Fingerprint

Angiopoietin-1
Acute Lung Injury
Hydrogen Peroxide
Blood Vessels
Hypoxia-Inducible Factor 1
Reactive Oxygen Species
Capillary Permeability
Lung
Inhalation
Vascular Endothelial Growth Factor A
Respiratory Hypersensitivity
Pneumonia
Tissue
Plasmas
Phosphorylation
1-Phosphatidylinositol 4-Kinase
Vascular Cell Adhesion Molecule-1
Endothelial cells
Intercellular Adhesion Molecule-1
Nuclear Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury. / So, Ri Kim; Kyung, Sun Lee; Seoung, Ju Park; Min, Kyung-Hoon; Ka, Young Lee; Yeong, Hun Choe; Sang, Hyun Hong; Gou, Young Koh; Yong, Chul Lee.

In: Experimental and Molecular Medicine, Vol. 40, No. 3, 30.06.2008, p. 320-331.

Research output: Contribution to journalArticle

So, RK, Kyung, SL, Seoung, JP, Min, K-H, Ka, YL, Yeong, HC, Sang, HH, Gou, YK & Yong, CL 2008, 'Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury', Experimental and Molecular Medicine, vol. 40, no. 3, pp. 320-331. https://doi.org/10.3858/emm.2008.40.3.320
So, Ri Kim ; Kyung, Sun Lee ; Seoung, Ju Park ; Min, Kyung-Hoon ; Ka, Young Lee ; Yeong, Hun Choe ; Sang, Hyun Hong ; Gou, Young Koh ; Yong, Chul Lee. / Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury. In: Experimental and Molecular Medicine. 2008 ; Vol. 40, No. 3. pp. 320-331.
@article{f0f65d0cfed348b498063f030867a297,
title = "Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury",
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.",
keywords = "Angiopoietin-1, Capillary permeability, COMP-Ang1 fusion protein, Hydrogen peroxide, Lung, Pneumonia, Reactive oxygen species, Vascular endothelial growth factor A",
author = "So, {Ri Kim} and Kyung, {Sun Lee} and Seoung, {Ju Park} and Kyung-Hoon Min and Ka, {Young Lee} and Yeong, {Hun Choe} and Sang, {Hyun Hong} and Gou, {Young Koh} and Yong, {Chul Lee}",
year = "2008",
month = "6",
day = "30",
doi = "10.3858/emm.2008.40.3.320",
language = "English",
volume = "40",
pages = "320--331",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "3",

}

TY - JOUR

T1 - Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

AU - So, Ri Kim

AU - Kyung, Sun Lee

AU - Seoung, Ju Park

AU - Min, Kyung-Hoon

AU - Ka, Young Lee

AU - Yeong, Hun Choe

AU - Sang, Hyun Hong

AU - Gou, Young Koh

AU - Yong, Chul Lee

PY - 2008/6/30

Y1 - 2008/6/30

N2 - 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.

AB - 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.

KW - Angiopoietin-1

KW - Capillary permeability

KW - COMP-Ang1 fusion protein

KW - Hydrogen peroxide

KW - Lung

KW - Pneumonia

KW - Reactive oxygen species

KW - Vascular endothelial growth factor A

UR - http://www.scopus.com/inward/record.url?scp=46449133564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46449133564&partnerID=8YFLogxK

U2 - 10.3858/emm.2008.40.3.320

DO - 10.3858/emm.2008.40.3.320

M3 - Article

VL - 40

SP - 320

EP - 331

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 3

ER -