Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation
Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation
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DOI：
10.1182/blood-2009-05-222364
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发表时间：
2009-12-03
期刊：
影响因子：
20.3
通讯作者：
Davis, George E.
中科院分区：
文献类型：
--
作者：
Stratman, Amber N.;Malotte, Kristine M.;Davis, George E.
我们发现内皮细胞（EC）产生的血管引导通道（即在管形成过程中产生的基质空间）作为沿EC管腔表面的周细胞募集和运动的通道，促进血管成熟事件，包括血管基底膜基质组装和EC管直径限制。在鹌鹑发育过程中，周细胞沿微血管募集与血管基底膜基质沉积直接相关。周细胞募集到EC管导致特异性诱导纤维连接蛋白和nidogen-1（即连接基底膜组分的基质桥接蛋白）以及perlecan和层粘连蛋白同种异构体。与这些事件一致的是，整合素α (5) β(1)、α (3) β(1)、α (6) β(1)和α (1) β(1)的上调发生在ec -周细胞共培养中，但不只是ec培养。整合素α (5) β(1)、α (3) β(1)、α (6) β(1)和α (1) β(1)结合纤维连接蛋白、氮化原、层粘连蛋白同型异构体和IV型胶原。针对这些受体的整合素阻断抗体、纤维连接蛋白基质组装的破坏以及周细胞组织金属蛋白酶抑制剂(TIMP)-3（一种已知的血管管稳定调节剂）的小干扰RNA抑制都导致EC基膜减少，导致血管管腔直径增加，这是EC-周细胞相互作用功能失调的关键指标。因此，在血管形成过程中，周细胞聚集到ec内衬管是一个控制血管基底膜基质组装的刺激事件，是调节血管形态发生向稳定过渡的基本成熟步骤。（血液，2009;114:5091-5101）
We show that endothelial cell (EC)-generated vascular guidance tunnels (ie, matrix spaces created during tube formation) serve as conduits for the recruitment and motility of pericytes along EC ablumenal surfaces to facilitate vessel maturation events, including vascular basement membrane matrix assembly and restriction of EC tube diameter. During quail development, pericyte recruitment along microvascular tubes directly correlates with vascular basement membrane matrix deposition. Pericyte recruitment to EC tubes leads to specific induction of fibronectin and nidogen-1 (ie, matrix-bridging proteins that link together basement membrane components) as well as perlecan and laminin isoforms. Coincident with these events, up-regulation of integrins, alpha(5)beta(1), alpha(3)beta(1), alpha(6)beta(1), and alpha(1)beta(1), which bind fibronectin, nidogens, laminin isoforms, and collagen type IV, occurs in EC-pericyte cocultures, but not EC-only cultures. Integrin-blocking antibodies to these receptors, disruption of fibronectin matrix assembly, and small interfering RNA suppression of pericyte tissue inhibitor of metalloproteinase (TIMP)-3 (a known regulator of vascular tube stabilization) all lead to decreased EC basement membrane, resulting in increased vessel lumen diameter, a key indicator of dysfunctional EC-pericyte interactions. Thus, pericyte recruitment to EC-lined tubes during vasculogenesis is a stimulatory event controlling vascular basement membrane matrix assembly, a fundamental maturation step regulating the transition from vascular morphogenesis to stabilization. (Blood. 2009; 114: 5091-5101)