EMILIN1/α9β1 Integrin Interaction Is Crucial in Lymphatic Valve Formation and Maintenance
EMILIN1/α9β1 Integrin Interaction Is Crucial in Lymphatic Valve Formation and Maintenance
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DOI：
10.1128/mcb.00872-13
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发表时间：
2013-11-01
影响因子：
5.3
通讯作者：
Spessotto, Paola
中科院分区：
文献类型：
--
作者：
Danussi, Carla;Belluz, Lisa Del Bel;Spessotto, Paola
淋巴管在维持组织间质液平衡中起着至关重要的作用。功能性集合淋巴管在淋巴转运中的作用最近在导致水肿的病理学中得到了强调，目前还没有治疗方法。腔内瓣膜在此过程中至关重要。然而，瓣膜的形成和成熟尚未完全阐明，特别是细胞外基质（ECM）所起的作用。我们假设EMILIN 1是一种ECM多结构域糖蛋白，调节淋巴瓣的形成和维持。使用小鼠基因敲除模型，我们表明，在缺乏EMILIN 1，小鼠表现出淋巴管结构和淋巴流量的缺陷。通过应用形态测定在体外和体内功能测定，我们得出结论，这种受损的表型依赖于缺乏α 9 β 1整合素的参与，特定的淋巴管内皮细胞受体EMILIN 1，以及随后的细胞增殖和迁移的紊乱。我们的数据表明，EMILIN 1-整合素α 9相互作用在淋巴管系统，特别是在淋巴管瓣的形成和维护中的基本作用，并强调了这种ECM组分在显示增殖调节功能和作为淋巴管内皮细胞迁移中的“引导”分子的重要性。
Lymphatic vasculature plays a crucial role in the maintenance of tissue interstitial fluid balance. The role of functional collecting lymphatic vessels in lymph transport has been recently highlighted in pathologies leading to lymphedema, for which treatments are currently unavailable. Intraluminal valves are of paramount importance in this process. However, valve formation and maturation have not been entirely elucidated yet, in particular, the role played by the extracellular matrix ( ECM). We hypothesized that EMILIN1, an ECM multidomain glycoprotein, regulates lymphatic valve formation and maintenance. Using a mouse knockout model, we show that in the absence of EMILIN1, mice exhibit defects in lymphatic valve structure and in lymph flow. By applying morphometric in vitro and in vivo functional assays, we conclude that this impaired phenotype depends on the lack of alpha 9 beta 1 integrin engagement, the specific lymphatic endothelial cell receptor for EMILIN1, and the ensuing derangement of cell proliferation and migration. Our data demonstrate a fundamental role for EMILIN1-integrin alpha 9 interaction in lymphatic vasculature, especially in lymphatic valve formation and maintenance, and underline the importance of this ECM component in displaying a regulatory function in proliferation and acting as a "guiding" molecule in migration of lymphatic endothelial cells.