Critical roles for murine Reck in the regulation of vascular patterning and stabilization.
Critical roles for murine Reck in the regulation of vascular patterning and stabilization.
复制标题
DOI：
10.1038/srep17860
复制
发表时间：
2015-12-11
影响因子：
4.6
通讯作者：
Noda M
中科院分区：
文献类型：
--
作者：
de Almeida GM;Yamamoto M;Morioka Y;Ogawa S;Matsuzaki T;Noda M
细胞外基质（ECM）在血管发育中起着重要作用，但其分子机制尚不清楚。RECK是一种在多种癌症中下调的肿瘤抑制因子，编码一种膜锚定基质金属蛋白酶调节因子。缺乏功能性Reck的小鼠在子宫内死亡，证明其对哺乳动物胚胎发育的重要性;然而，妊娠中期致死的根本原因仍不清楚。使用Reck条件性基因敲除小鼠，我们现在已经证明，血管壁细胞中缺乏Reck是妊娠中期致死的主要原因。使用培养的主动脉外植体的实验进一步揭示，Reck对于萌芽血管生成中的至少两个事件是必不可少的：（1）壁和内皮尖端细胞与微血管的正确结合和（2）维持血管周围的纤连蛋白基质。这些发现证明了适当的细胞-细胞相互作用和ECM维持对于血管生成的重要性，以及Reck作为这些事件的关键调节剂的参与。
Extracellular matrix (ECM) is known to play several important roles in vascular development, although the molecular mechanisms behind these remain largely unknown. RECK, a tumor suppressor downregulated in a wide variety of cancers, encodes a membrane-anchored matrix-metalloproteinase-regulator. Mice lacking functional Reck die in utero, demonstrating its importance for mammalian embryogenesis; however, the underlying causes of mid-gestation lethality remain unclear. Using Reck conditional knockout mice, we have now demonstrated that the lack of Reck in vascular mural cells is largely responsible for mid-gestation lethality. Experiments using cultured aortic explants further revealed that Reck is essential for at least two events in sprouting angiogenesis; (1) correct association of mural and endothelial tip cells to the microvessels and (2) maintenance of fibronectin matrix surrounding the vessels. These findings demonstrate the importance of appropriate cell-cell interactions and ECM maintenance for angiogenesis and the involvement of Reck as a critical regulator of these events.