Divergent roles of prokineticin receptors in the endothelial cells: angiogenesis and fenestration
Divergent roles of prokineticin receptors in the endothelial cells: angiogenesis and fenestration
复制标题
DOI：
10.1152/ajpheart.00898.2009
复制
发表时间：
2010-03-01
影响因子：
4.8
通讯作者：
Nebigil, Canan G.
中科院分区：
文献类型：
--
作者：
Guilini, Celia;Urayama, Kyoji;Nebigil, Canan G.
Guilini C，Urayama K，Turkeri G，Dedeoglu DB，Kurose H，Messaddeq N，Nebigil CG.前动力素受体在内皮细胞中的不同作用：血管生成和开窗。Am J Physiol Heart Circ Physiol 298：H844-H852，2010.首次发表于2009年12月18日; doi：10.1152/ajpheart.00898.2009。前动力素是激活两种G蛋白偶联受体PKR 1和PKR 2的分泌肽。前动力素诱导血管生成和开窗，但参与这些功能的同源受体是未知的。我们假设前动力素受体信号通路和表达谱在决定前动力素对冠状动脉内皮细胞（H5 V）的选择性作用中的作用。PKR 1/MAPK/Akt信号通路的激活刺激H5 V细胞的增殖、迁移和血管生成，其中PKR 1比PKR 2占优势。PKR 1与G（α 11）共定位，并在用前动力蛋白-2刺激这些细胞后内化。H5 V细胞中PKR 1或G（α 11）表达的敲低有效地抑制了prokineticin-2诱导的血管形成和MAPK/Akt激活，表明PKR 1/G（α 11）在此过程中的作用。然而，在PKR 2超过PKR 1占优势的条件下，这些细胞显示出有孔内皮细胞表型。PKR 2过表达的H5 V细胞显示大量的多泡体和小窝簇，以及闭合小带-1紧密连接蛋白分布的破坏。前动力蛋白-2诱导PKR 2与G（α 12）共定位，并激活G（α 12），G（α 12）结合于闭锁小带-1以触发该蛋白在这些细胞中的降解。前动力蛋白-2诱导仅表达PKR 1的人主动脉内皮细胞形成血管样结构，并破坏仅表达PKR 2的人肝窦内皮细胞的紧密连接，证实了这些受体的不同作用。我们的研究结果表明，冠状动脉内皮细胞的功能特性取决于PKR 1和PKR 2的表达水平和这些受体所使用的不同信号通路。
Guilini C, Urayama K, Turkeri G, Dedeoglu DB, Kurose H, Messaddeq N, Nebigil CG. Divergent roles of prokineticin receptors in the endothelial cells: angiogenesis and fenestration. Am J Physiol Heart Circ Physiol 298: H844-H852, 2010. First published December 18, 2009; doi:10.1152/ajpheart.00898.2009.-Prokineticins are secreted peptides that activate two G protein-coupled receptors: PKR1 and PKR2. Prokineticins induce angiogenesis and fenestration, but the cognate receptors involved in these functions are unknown. We hypothesized a role for prokineticin receptor signaling pathways and expression profiles in determining the selective effects of prokineticins on coronary endothelial cells (H5V). Activation of the PKR1/MAPK/Akt signaling pathway stimulates proliferation, migration, and angiogenesis in H5V cells, in which PKR1 predominates over PKR2. PKR1 was colocalized with G(alpha 11) and was internalized following the stimulation of these cells with prokineticin-2. Knock down of PKR1 or G(alpha 11) expression in H5V cells effectively inhibited prokineticin-2-induced vessel formation and MAPK/Akt activation, indicating a role for PKR1/G(alpha 11) in this process. However, in conditions in which PKR2 predominated over PKR1, these cells displayed a fenestrated endothelial cell phenotype. H5V cells overexpressing PKR2 displayed large numbers of multivesicular bodies and caveolar clusters and a disruption of the distribution of zonula occluden-1 tight junction protein. Prokineticin-2 induced the colocalization of PKR2 with G(alpha 12), and activated G(alpha 12), which bound to zonula occluden-1 to trigger the degradation of this protein in these cells. Prokineticin-2 induced the formation of vessel-like structures by human aortic endothelial cells expressing only PKR1, and disorganized the tight junctions in human hepatic sinusoidal endothelial cells expressing only PKR2, confirming the divergent roles of these receptors. Our findings show the functional characteristics of coronary endothelial cells depend on the expression of PKR1 and PKR2 levels and the divergent signaling pathways used by these receptors.