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

25 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

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hato, T., Kimura, Y., Morisada, T., Koh, G. Y., 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, 381(2), 218-223. https://doi.org/10.1016/j.bbrc.2009.02.030