Research press release


Nature Medicine

Inhibiting lymphatic vessel growth



J Ambatiたちは、このような阻害因子の存在を明らかにした。この可溶性Vegfr-2とよばれる因子は、Vegfタンパク質の情報伝達を妨げることによってリンパ管形成を阻害する。マウスでは、組織特異的に可溶性Vegfr-2を失わせると、正常ならリンパ管をもたないはずの核膜などにも、リンパ系が自発的に形成される。外傷や移植後に可溶性Vegfr-2を投与すると、リンパ管形成は阻害されるが血管形成は阻害されず、移植手術後のマウスの生存率が上昇した。


The discovery of the first endogenous inhibitor of lymphatic vessel growth is reported in this week's Nature Medicine. The finding could potentially lead to treatment in cases of transplantation rejection and lymph vessel growth in tumours.

The lymphatic system is crucial in transporting fluids and molecules to cells as well as draining unwanted fluids. ?The disruption of the balance between positive and negative regulators for blood and lymphatic vessel growth can lead to many diseases, such as. Although many natural inhibitors of blood vessel growth exist, an endogenous selective inhibitor of lymphatic vessel growth ― lymphangiogenesis ― had previously not been described.

Jayakrishna Ambati and his colleagues report the existence of such an inhibitor, called soluble Vegfr-2. Soluble Vegfr-2 inhibits lymphangiogenesis by blocking signaling of the protein Vegf. In mice, tissue-specific loss of soluble Vegfr-2 induced spontaneous growth of lymphatic system to structures that normally lack lymphatic vessels, such as the cornea. Administration of soluble Vegfr-2 after injury or transplantation also inhibited lymphangiogenesis but not blood vessel growth, and therefore enhanced mice's survival after graft surgery.

Owing to the selective effects of soluble Vegfr-2 on lymphatic vessels while sparing blood vessels, it might lead to potential treatments for lymphatic vascular malformations, transplantation rejection and tumor lymphangiogenesis.

doi: 10.1038/nm.2018


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