A role for planar cell polarity signaling in angiogenesis
A role for planar cell polarity signaling in angiogenesis
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DOI：
10.1007/s10456-008-9116-2
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发表时间：
2008-12-01
期刊：
影响因子：
9.8
通讯作者：
Crews, Craig M.
中科院分区：
文献类型：
--
作者：
Cirone, Pasquale;Lin, Shengda;Crews, Craig M.
平面细胞极性（PCP）通路是一个高度保守的信号级联，在发育过程中协调上皮和轴突形态发生运动。血管生成也涉及极化细胞的生长和迁移，尽管其细胞间通讯的机制尚不清楚。在这里，通过细胞培养实验，我们证明PCP信号的抑制会破坏内皮细胞的生长、极性和迁移，所有这些都可以通过下游Daam-1、Diversin或Inversin的表达来激活该途径。沉默Dvl2或Prickle均可抑制内皮细胞的增殖。此外，p53的缺失挽救了内皮细胞生长停滞，而不是PCP破坏引起的迁移抑制。此外，我们发现斑马鱼Wnt5突变体（管尾（ppt））， PCP信号受损，表现出血管发育缺陷。这些发现揭示了PCP信号在内皮细胞协调组装成血管结构中的潜在作用，并对发育和疾病中的血管重塑具有重要意义。
The planar cell polarity (PCP) pathway is a highly conserved signaling cascade that coordinates both epithelial and axonal morphogenic movements during development. Angiogenesis also involves the growth and migration of polarized cells, although the mechanisms underlying their intercellular communication are poorly understood. Here, using cell culture assays, we demonstrate that inhibition of PCP signaling disrupts endothelial cell growth, polarity, and migration, all of which can be rescued through downstream activation of this pathway by expression of either Daam-1, Diversin or Inversin. Silencing of either Dvl2 or Prickle suppressed endothelial cell proliferation. Moreover, loss of p53 rescues endothelial cell growth arrest but not the migration inhibition caused by PCP disruption. In addition, we show that the zebrafish Wnt5 mutant (pipetail (ppt)), which has impaired PCP signaling, displays vascular developmental defects. These findings reveal a potential role for PCP signaling in the coordinated assembly of endothelial cells into vascular structures and have important implications for vascular remodeling in development and disease.