Fibulin-5/DANCE is essential for elastogenesis in vivo
Fibulin-5/DANCE is essential for elastogenesis in vivo
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DOI：
10.1038/415171a
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发表时间：
2002-01-10
期刊：
影响因子：
64.8
通讯作者：
Chien, KR
中科院分区：
文献类型：
--
作者：
Nakamura, T;Lozano, PR;Chien, KR
弹性纤维系统在需要弹性的各种器官（如大动脉、肺和皮肤）的结构和功能中起主要作用（1,2）。虽然已知弹性纤维是由微纤维蛋白（如纤原蛋白和潜伏转化生长因子(TGF)- β结合蛋白）和聚合弹性蛋白组成，但其组装和发育的机制尚不清楚。在这里，我们报道了纤维蛋白-5（也称为DANCE），一种最近发现的整合素配体(3)，是弹性纤维组织的重要决定因素。通过基因靶向产生的纤维蛋白-5（-/-）小鼠在全身表现出严重紊乱的弹性纤维系统。Fibulin-5（-/-）小鼠存活至成年，但主动脉弯曲，失去顺应性，严重肺气肿，皮肤松弛（皮肤松弛）。这些组织含有破碎的弹性蛋白，但弹性酶活性没有增加，表明弹性纤维发育有缺陷。Fibulin-5在体外直接与弹性纤维相互作用，并通过其氨基末端结构域作为细胞表面整合素alphav beta3、alphav beta5和alpha9 beta1的配体。因此，纤维蛋白-5可能为细胞提供弹性纤维的锚定，从而稳定和组织皮肤、肺和脉管系统中的弹性纤维。
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin(1,2). Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta -binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand(3), is an essential determinant of elastic fibre organization. fibulin-5(-/-) mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5(-/-) mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphav beta3, alphav beta5 and alpha9 beta1 through its aminoterminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature.