Angiomotin-like2 Gene (amotl2) Is Required for Migration and Proliferation of Endothelial Cells during Angiogenesis*
Angiomotin-like2 Gene (amotl2) Is Required for Migration and Proliferation of Endothelial Cells during Angiogenesis*
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DOI：
10.1074/jbc.m111.296806
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Yeqi Wang;Zhiqiang Li;Pengfei Xu;Lei Huang;Jingyuan Tong;Huizhe Huang;A. Meng
中科院分区：
文献类型：
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作者：
Yeqi Wang;Zhiqiang Li;Pengfei Xu;Lei Huang;Jingyuan Tong;Huizhe Huang;A. Meng
背景：Amotl2在血管中表达，但其在血管形成中的功能尚不清楚。结果：Amotl2敲低会损害斑马鱼胚胎的节间血管生长和人内皮细胞的试管形成。结论：Amotl2通过与MAPK激活相关的方式调节细胞极性、迁移和增殖，是血管生成所必需的。意义：Amotl2在血管生成过程中调控内皮细胞的多种行为中发挥重要作用。血管生成包括内皮细胞的发芽、迁移和增殖。血管运动素样2基因（amotl2）已在斑马鱼胚胎血管中发现，但其在血管生成中的功能及其潜在机制尚不清楚。在这项研究中，我们证明了在斑马鱼Tg(fli1:EGFP)y1和Tg(fli1:nEGFP)y7转基因胚胎中，amotl2的敲低会损害节间血管的生长并抑制内皮细胞的增殖。移植实验表明，amotl2在节间血管生长中的功能是细胞自主的。AMOTL2敲低在培养的人脐静脉内皮细胞中也抑制细胞增殖和迁移，破坏细胞极性，最终中断血管管样结构的形成。Amotl2通过c-Src促进MAPK/ERK活化，这依赖于103位酪氨酸残基的磷酸化，但不依赖于c端pdz结合域。综上所述，我们的数据表明，Amotl2在血管生成内皮细胞的极性、迁移和增殖中起着关键作用。
Background: Amotl2 is expressed in blood vessels, but its function in vasculature formation is unknown. Results: Amotl2 knockdown impairs intersegmental vessel growth in zebrafish embryos and in vitro tube formation of human endothelial cells. Conclusion: Amotl2 is required for angiogenesis by regulating cell polarity, migration, and proliferation in a way related to MAPK activation. Significance: Amotl2 plays important roles in regulating multiple behaviors of endothelial cells during angiogenesis. Angiogenesis involves sprouting, migration, and proliferation of endothelial cells. The angiomotin-like2 gene (amotl2) has been found in blood vessels in zebrafish embryos, but its function in angiogenesis and underlying mechanisms remain unknown. In this study, we demonstrate that knockdown of amotl2 in zebrafish Tg(fli1:EGFP)y1 and Tg(fli1:nEGFP)y7 transgenic embryos impairs the intersegmental vessel growth and suppresses proliferation of endothelial cells. Transplantation experiments indicate that function of amotl2 in intersegmental vessel growth is cell-autonomous. AMOTL2 knockdown in cultured human umbilical vein endothelial cells also inhibits cell proliferation and migration and disrupts cell polarity, ultimately interrupting the formation of vascular tube-like structures. Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain. Taking together, our data indicate that Amotl2 plays a pivotal role in polarity, migration and proliferation of angiogenic endothelial cells.