Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism.

Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism.
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DOI:
10.1016/j.devcel.2009.12.006
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发表时间:
2010-01-19
期刊:
影响因子:
11.8
通讯作者:
Iruela-Arispe ML
Iruela-Arispe ML
中科院分区:
生物学1区
文献类型:
--
作者:
Zovein AC;Luque A;Turlo KA;Hofmann JJ;Yee KM;Becker MS;Fassler R;Mellman I;Lane TF;Iruela-Arispe ML

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维持单层内皮细胞、鳞状内皮细胞形状和形成开放的血管腔都需要明确的内皮细胞极性。新生血管内皮细胞中β1整合素(Itgb1)的丢失会导致动脉内皮细胞极化和管腔形成的破坏。极性的丧失表现为立方形内皮细胞,正常极化的细胞-细胞黏附分子水平失调和定位错误,以及极性基因PARD3(PARD3)的表达减少。β-1整合素和PAR3均定位于内皮层,PAR3在动脉内皮细胞中优先表达。管腔闭塞也仅见于动脉,通过替换β1缺乏的血管中的PAR3蛋白可以部分挽救。综上所述,我们的发现表明,β1整合素在PAR3的上游发挥作用,是内皮细胞极性和管腔形成所需的分子级联的一部分。
Maintenance of single layered endothelium, squamous endothelial cell shape, and formation of a patent vascular lumen all require defined endothelial cell polarity. Loss of β1 integrin (Itgb1) in nascent endothelium leads to disruption of arterial endothelial cell polarity and lumen formation. The loss of polarity is manifested as cuboidal shaped endothelial cells, dysregulated levels and mis-localization of normally polarized cell-cell adhesion molecules, as well as decreased expression of the polarity gene Par3 (pard3). β1 integrin and Par3 are both localized to the endothelial layer, with preferential expression of Par3 in arterial endothelium. Luminal occlusion is also exclusively noted in arteries, and is partially rescued by replacement of Par3 protein in β1 deficient vessels. Combined, our findings demonstrate that β1 integrin functions upstream of Par3 as part of a molecular cascade required for endothelial cell polarity and lumen formation.
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