Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth.
Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth.
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血管和淋巴管的正负分子调节的精确平衡的破坏可能会导致无数的疾病，这些疾病影响着全世界四分之一的人。虽然已经鉴定了几十种天然的血管生成抑制物，但尚未描述一种内源性选择性淋巴管抑制物。我们报道存在一种分泌的、剪接的血管内皮生长因子受体-2(sVegfr-2)，它通过阻断血管内皮生长因子-c来抑制发育和修复性淋巴管的生成。在小鼠出生时，组织特异性的sVegfr-2丢失导致正常淋巴性角膜的自发淋巴管入侵和皮肤淋巴管的增生，而不伴随血管系统的变化。SVegfr-2抑制角膜缝线损伤或移植诱导的淋巴管生成，但不抑制血管生成，提高角膜移植物存活率，抑制淋巴管瘤细胞增殖。天然产生的sVegfr-2是一种血管和淋巴管的分子解偶联分子，它的调节可能在淋巴管畸形、移植，以及潜在的肿瘤淋巴管生成和淋巴水肿中发挥治疗作用。
Disruption of the precise balance of positive and negative molecular regulators of blood and lymphatic vessels can lead to myriad diseases that affect one in four people worldwide. Although dozens of natural inhibitors of hemangiogenesis have been identified, an endogenous selective inhibitor of lymphatic vessels has not yet been described. We report the existence of a secreted, splice variant of vascular endothelial growth factor receptor-2 (sVegfr-2) that inhibits developmental and reparative lymphangiogenesis by blocking Vegf-c. Tissue-specific loss of sVegfr-2 in mice induced, at birth, spontaneous lymphatic invasion of the normally alymphatic cornea and hyperplasia of skin lymphatics without accompanying changes in blood vasculature. sVegfr-2 inhibited lymphangiogenesis but not hemangiogenesis induced by corneal suture injury or transplantation, enhanced corneal allograft survival, and suppressed lymphangioma cellular proliferation. Naturally occurring sVegfr-2 is a molecular uncoupler of blood and lymphatic vessels whose modulation might have a therapeutic role in lymphatic vascular malformations, transplantation, and potentially in tumor lymphangiogenesis and lymphedema.
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DOI：
10.1093/jnci/94.11.819
发表时间：
2002-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
He, YL;Kozaki, KI;Alitalo, K
通讯作者：
Alitalo, K
影响因子：
20.3
作者：
Hirakawa, Satoshi;Brown, Lawrence F.;Detmar, Michael
通讯作者：
Detmar, Michael
影响因子：
2.8
作者：
Cursiefen, C;Chen, L;Streilein, JW
通讯作者：
Streilein, JW
影响因子：
4
作者：
Bernatchez, PN;Rollin, S;Sirois, MG
通讯作者：
Sirois, MG
DOI：
10.1073/pnas.0708148104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Ebos, John M. L.;Lee, Christina R.;Kerbel, Robert S.
通讯作者：
Kerbel, Robert S.