The role of Ang/Tie signaling in lymphangiogenesis.
The angiopoietin/Tie system plays a key role in remodeling and maturation of blood vessels as well as lymphatic vessels. The angiopoietin family includes four ligands (Ang-1, Ang-2 and Ang-3/4) and two corresponding tyrosine kinase receptors (Tie1 and Tie2). The best characterized angiopoietins are Ang-1 and Ang-2. Ang-1 acts as an obligate agonist of the Tie2 receptor. Binding of Ang-1 to Tie2 induces its autophosphorylation and promotes vascular stability and integrity. Ang-1 induces lymphatic vessel enlargement, sprouting and proliferation in a VEGFR-3-dependent manner. In contrast, whether Ang-2 is agonistic or antagonistic is dependent on dose and context. Ang-2 modulates angiogenesis in a cooperative manner with another important angiogenic factor, vascular endothelial growth factor A. In the presence of VEGF-A, Ang-2 promotes vascular sprouting. When in the absence of VEGF-A, Ang-2 induces vascular regression. However, genetic studies have revealed that Ang-2-deficient mice exhibit more severe defects in the lymphatic vasculature than in blood vessels. Ang-2 seems to be involved in the remodeling and stabilization of lymphatic vessels. Although the Ang/Tie system is essential for blood and lymphatic vessel remodeling and maturation, defining its precise role in blood and lymphatic development has been a major challenge. This review provides an update on our current understanding of the angiopoietin/Tie system in lymphangiogenesis.
Wu
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Lymphology Center of Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, People's Republic of China.
Liu
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N
D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D051379:Mice; D042787:Receptor, TIE-2 / Q000378:metabolism*; D015398:Signal Transduction
D042682:Angiopoietins; D042787:Receptor, TIE-2