Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation

Toru Morisada, Yuichi Oike, Yoshihiro Yamada, Takashi Urano, Masaki Akao, Yoshiaki Kubota, Hiromitsu Maekawa, Yoshishige Kimura, Masako Ohmura, Takeshi Miyamoto, Shiro Nozawa, Gou Young Koh, Kari Alitalo, Toshio Suda

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177 Citations (Scopus)

Abstract

Angiopoietin (Ang) signaling plays a role in angiogenesis and remodeling of blood vessels through the receptor tyrosine kinase Tie2, which is expressed on blood vessel endothelial cells (BECs). Recently it has been shown that Ang-2 is crucial for the formation of lymphatic vasculature and that defects in lymphangiogenesis seen in Ang-2 mutant mice are rescued by Ang-1. These findings suggest important roles for Ang signaling in the lymphatic vessel system; however, Ang function in lymphangiogenesis has not been characterized. In this study, we reveal that lymphatic vascular endothelial hyaluronan receptor 1-positive (LYVE-1+) lymphatic endothelial cells (LECs) express Tie2 in both embryonic and adult settings, indicating that Ang signaling occurs in lymphatic vessels. Therefore, we examined whether Ang-1 acts on in vivo lymphatic angiogenesis and in vitro growth of LECs. A chimeric form of Ang-1, cartilage oligomeric matrix protein (COMP)-Ang-1, promotes in vivo lymphatic angiogenesis in mouse cornea. Moreover, we found that COMP-Ang-1 stimulates in vitro colony formation of LECs. These Ang-1-induced in vivo and in vitro effects on LECs were suppressed by soluble Tie2-Fc fusion protein, which acts as an inhibitor by sequestering Ang-1. On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2.

Original languageEnglish
Pages (from-to)4649-4656
Number of pages8
JournalBlood
Volume105
Issue number12
DOIs
Publication statusPublished - 2005 Jun 15
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Morisada, T., Oike, Y., Yamada, Y., Urano, T., Akao, M., Kubota, Y., Maekawa, H., Kimura, Y., Ohmura, M., Miyamoto, T., Nozawa, S., Koh, G. Y., Alitalo, K., & Suda, T. (2005). Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation. Blood, 105(12), 4649-4656. https://doi.org/10.1182/blood-2004-08-3382