Angiopoietins contribute to lung development by regulating pulmonary vascular network formation

Tai Hato, Yoshishige Kimura, Tohru Morisada, Gou Young Koh, Keishi Miyata, Mitsuhisa Tabata, Tsuyoshi Kadomatsu, Motoyoshi Endo, Takashi Urano, Fumio Arai, Kimi Araki, Toshio Suda, Koichi Kobayashi, Yuichi Oike

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Angiopoietin (Ang) signaling through the Tie2 receptor regulates vasculature. The role of Ang signaling in pulmonary hypertension is well investigated, but its role in lung development is not elucidated. Here, we show that the Tie2 agonist ligand, Ang1, was detected in lung tissue at birth and its expression gradually increased in mice, whereas its antagonist Ang2 was abundant at birth and decreased inversely with Ang1. Mice expressing the potent chimeric Ang1 protein COMP-Ang1 in surfactant protein C (SPC)-positive lung epithelial cells, showed 50% lethality at birth due to respiratory failure. Surviving mice displayed impaired adaptive responsive respiratory function. Histological analysis revealed that pulmonary artery and alveolar structure were significantly dilated, and alveolar density was decreased to approximately a third of controls. Thus, the precise regulation of Tie2 signaling through an Ang1/Ang2 expression switch is important to construct a mature lung vascular network system required for normal lung development.

Original languageEnglish
Pages (from-to)218-223
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume381
Issue number2
DOIs
Publication statusPublished - Apr 3 2009
Externally publishedYes

Fingerprint

Angiopoietins
Blood Vessels
Lung
TIE-2 Receptor
Parturition
Protein C
Surface-Active Agents
Switches
Tissue
Ligands
Pulmonary Hypertension
Respiratory Insufficiency
Pulmonary Artery
Epithelial Cells
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Angiopoietins contribute to lung development by regulating pulmonary vascular network formation. / Hato, Tai; Kimura, Yoshishige; Morisada, Tohru; Koh, Gou Young; Miyata, Keishi; Tabata, Mitsuhisa; Kadomatsu, Tsuyoshi; Endo, Motoyoshi; Urano, Takashi; Arai, Fumio; Araki, Kimi; Suda, Toshio; Kobayashi, Koichi; Oike, Yuichi.

In: Biochemical and Biophysical Research Communications, Vol. 381, No. 2, 03.04.2009, p. 218-223.

Research output: Contribution to journalArticle

Hato, T, Kimura, Y, Morisada, T, Koh, GY, Miyata, K, Tabata, M, Kadomatsu, T, Endo, M, Urano, T, Arai, F, Araki, K, Suda, T, Kobayashi, K & Oike, Y 2009, 'Angiopoietins contribute to lung development by regulating pulmonary vascular network formation', Biochemical and Biophysical Research Communications, vol. 381, no. 2, pp. 218-223. https://doi.org/10.1016/j.bbrc.2009.02.030
Hato, Tai ; Kimura, Yoshishige ; Morisada, Tohru ; Koh, Gou Young ; Miyata, Keishi ; Tabata, Mitsuhisa ; Kadomatsu, Tsuyoshi ; Endo, Motoyoshi ; Urano, Takashi ; Arai, Fumio ; Araki, Kimi ; Suda, Toshio ; Kobayashi, Koichi ; Oike, Yuichi. / Angiopoietins contribute to lung development by regulating pulmonary vascular network formation. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 381, No. 2. pp. 218-223.
@article{f6088395a91a4476bb80504c179ce6dd,
title = "Angiopoietins contribute to lung development by regulating pulmonary vascular network formation",
abstract = "Angiopoietin (Ang) signaling through the Tie2 receptor regulates vasculature. The role of Ang signaling in pulmonary hypertension is well investigated, but its role in lung development is not elucidated. Here, we show that the Tie2 agonist ligand, Ang1, was detected in lung tissue at birth and its expression gradually increased in mice, whereas its antagonist Ang2 was abundant at birth and decreased inversely with Ang1. Mice expressing the potent chimeric Ang1 protein COMP-Ang1 in surfactant protein C (SPC)-positive lung epithelial cells, showed 50{\%} lethality at birth due to respiratory failure. Surviving mice displayed impaired adaptive responsive respiratory function. Histological analysis revealed that pulmonary artery and alveolar structure were significantly dilated, and alveolar density was decreased to approximately a third of controls. Thus, the precise regulation of Tie2 signaling through an Ang1/Ang2 expression switch is important to construct a mature lung vascular network system required for normal lung development.",
author = "Tai Hato and Yoshishige Kimura and Tohru Morisada and Koh, {Gou Young} and Keishi Miyata and Mitsuhisa Tabata and Tsuyoshi Kadomatsu and Motoyoshi Endo and Takashi Urano and Fumio Arai and Kimi Araki and Toshio Suda and Koichi Kobayashi and Yuichi Oike",
year = "2009",
month = "4",
day = "3",
doi = "10.1016/j.bbrc.2009.02.030",
language = "English",
volume = "381",
pages = "218--223",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Angiopoietins contribute to lung development by regulating pulmonary vascular network formation

AU - Hato, Tai

AU - Kimura, Yoshishige

AU - Morisada, Tohru

AU - Koh, Gou Young

AU - Miyata, Keishi

AU - Tabata, Mitsuhisa

AU - Kadomatsu, Tsuyoshi

AU - Endo, Motoyoshi

AU - Urano, Takashi

AU - Arai, Fumio

AU - Araki, Kimi

AU - Suda, Toshio

AU - Kobayashi, Koichi

AU - Oike, Yuichi

PY - 2009/4/3

Y1 - 2009/4/3

N2 - Angiopoietin (Ang) signaling through the Tie2 receptor regulates vasculature. The role of Ang signaling in pulmonary hypertension is well investigated, but its role in lung development is not elucidated. Here, we show that the Tie2 agonist ligand, Ang1, was detected in lung tissue at birth and its expression gradually increased in mice, whereas its antagonist Ang2 was abundant at birth and decreased inversely with Ang1. Mice expressing the potent chimeric Ang1 protein COMP-Ang1 in surfactant protein C (SPC)-positive lung epithelial cells, showed 50% lethality at birth due to respiratory failure. Surviving mice displayed impaired adaptive responsive respiratory function. Histological analysis revealed that pulmonary artery and alveolar structure were significantly dilated, and alveolar density was decreased to approximately a third of controls. Thus, the precise regulation of Tie2 signaling through an Ang1/Ang2 expression switch is important to construct a mature lung vascular network system required for normal lung development.

AB - Angiopoietin (Ang) signaling through the Tie2 receptor regulates vasculature. The role of Ang signaling in pulmonary hypertension is well investigated, but its role in lung development is not elucidated. Here, we show that the Tie2 agonist ligand, Ang1, was detected in lung tissue at birth and its expression gradually increased in mice, whereas its antagonist Ang2 was abundant at birth and decreased inversely with Ang1. Mice expressing the potent chimeric Ang1 protein COMP-Ang1 in surfactant protein C (SPC)-positive lung epithelial cells, showed 50% lethality at birth due to respiratory failure. Surviving mice displayed impaired adaptive responsive respiratory function. Histological analysis revealed that pulmonary artery and alveolar structure were significantly dilated, and alveolar density was decreased to approximately a third of controls. Thus, the precise regulation of Tie2 signaling through an Ang1/Ang2 expression switch is important to construct a mature lung vascular network system required for normal lung development.

UR - http://www.scopus.com/inward/record.url?scp=61849108712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61849108712&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2009.02.030

DO - 10.1016/j.bbrc.2009.02.030

M3 - Article

VL - 381

SP - 218

EP - 223

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -