A critical role for calponin 2 in vascular development
A critical role for calponin 2 in vascular development
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DOI：
10.1074/jbc.m506991200
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发表时间：
2006-03-10
影响因子：
4.8
通讯作者：
Sukhatme, VP
中科院分区：
文献类型：
--
作者：
Tang, J;Hu, G;Sukhatme, VP
钙调蛋白2（h2 calponin，CNN 2）是一种与细胞骨架组织有关的肌动蛋白结合蛋白。我们发现，在斑马鱼（Danio rerio）发育过程中，受精后16至30 h，calponin 2的表达相对局限于脉管系统。48小时后，注射反义morpholino寡核苷酸对钙调蛋白2的胚胎在1 - 4-细胞阶段，斑马鱼表现出各种心血管缺陷，包括缓慢的轴向和头部循环，缺乏循环在节间血管和背纵吻合血管，扩大脑室，心包水肿，除了过度弯曲，螺旋形尾巴和尾鳍扭曲。在Tg（fli 1：EGFP）（y1）斑马鱼系（其中fli 1启动子驱动血管特异性增强的绿色荧光蛋白表达）中，钙调蛋白2的敲低表明钙调蛋白2表达的减少阻断了血管段间血管形成期间内皮细胞的适当迁移。体外研究表明，碱性成纤维细胞生长因子诱导的人脐静脉内皮细胞迁移下调敲低的钙调蛋白2表达，使用反义腺病毒，和钙调蛋白2的过度表达增强迁移和加速伤口愈合。这些事件与丝裂原活化蛋白激酶的激活相关;此外，抑制该途径阻断了钙调蛋白2的促迁移作用。总的来说，这些数据表明，钙调蛋白2在体内和体外内皮细胞的迁移中起着重要的作用，其表达对血管的正常发育至关重要。
Calponin 2 (h2 calponin, CNN2) is an actin-binding protein implicated in cytoskeletal organization. We have found that the expression of calponin 2 is relatively restricted to vasculature from 16 to 30 h post-fertilization during zebrafish ( Danio rerio) development. Forty-eight hours after injecting antisense morpholino oligos against calponin 2 into embryos at the 1 - 4-cell stage, zebrafish demonstrated various cardiovascular defects, including sluggish axial and head circulation, absence of circulation in intersegmental vessels and in the dorsal longitudinal anastomotic vessel, enlarged cerebral ventricles, and pericardial edema, in addition to an excess bending, spiraling tail and twisting of the caudal fin. Knockdown of calponin 2 in the Tg(fli1: EGFP)(y1) zebrafish line ( in which a fli1 promoter drives vascular-specific enhanced green fluorescent protein expression) indicated that diminished calponin 2 expression blocked the proper migration of endothelial cells during formation of intersegmental vessels. In vitro studies showed that basic fibroblast growth factor-induced human umbilical vein endothelial cell migration was down-regulated by knockdown of calponin 2 expression using an antisense adenovirus, and overexpression of calponin 2 enhanced migration and hastened wound healing. These events were correlated with activation of mitogen-activated protein kinase; moreover, inhibition of this pathway blocked the promigratory effect of calponin 2. Collectively, these data suggest that calponin 2 plays an important role in the migration of endothelial cells both in vivo and in vitro and that its expression is critical for proper vascular development.