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Circulation：TBX20通过前动力蛋白2-前动力蛋白受体1通路调控血管生成

2018-09-02 MedSci MedSci原创

血管生成TBX20PROK2PROKR1
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血管生成是胚胎发生的重要组成部分，靶向血管生成可改善患者的多种病理状况预后。TBX20是胚胎发育的重要转录因子，其缺陷与先天性心脏病相关。但TBX20在血管生成中的作用尚不明确。研究人员采用功能丧失性和功能获得性方法来探究TBX20在血管生成中的作用，并采用血管生成基因芯片鉴定TBX20的重要下游靶点。基因芯片显示敲低TBX20可明显降低血管生成相关PROK2（前动力蛋白2）基因的表达。敲除TBX

血管生成是胚胎发生的重要组成部分，靶向血管生成可改善患者的多种病理状况预后。TBX20是胚胎发育的重要转录因子，其缺陷与先天性心脏病相关。但TBX20在血管生成中的作用尚不明确。

研究人员采用功能丧失性和功能获得性方法来探究TBX20在血管生成中的作用，并采用血管生成基因芯片鉴定TBX20的重要下游靶点。

基因芯片显示敲低TBX20可明显降低血管生成相关PROK2（前动力蛋白2）基因的表达。敲除TBX20会阻碍内皮细胞迁移，和体外血管形成。在血管生成的小鼠模型中，研究人员在小鼠皮下植入基质凝胶栓，发现TBX20缺陷可显著降低PROK2的表达，并限制腔内血管生成。

此外，重组PROK2管理可增强后肢缺血小鼠的血管生成能力、促进血流恢复。在斑马鱼中，用吗啡反义寡核苷酸一过性敲低tbx20或用CRISPR/Case9破坏tbx20基因来干扰血管生成。而且，丢失prok2或其同源受体prokr1a也可限制血管生成。相反，过表达prok2或prokr1a可恢复tbx20缺陷动物的血管生成。

本研究表明TBX20作为新的转录因子，可在发育和疾病过程中通过PROK2-PROKR1通路调控血管生成，揭示了血管生成调控的一种新模式，即TBX20-PROK2-PROKR1信号级联可做做“生物电容器”转导并维持血管内皮细胞生长因子的促血管生成效应。该通路或可作为血管生成障碍疾病的治疗靶点。



原始出处：

Shu Meng， Qilin Gu，et al. TBX20 Regulates Angiogenesis Through the Prokineticin 2–Prokineticin Receptor 1 Pathway. Circulation. 2018；138：913-928

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    2018-09-03 hwqiang

    好

    0

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    2018-09-03 kafei

    学习了谢谢

    0

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    2018-09-03 smartxiuxiu

    好

    0

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    2018-09-02 惠映实验室

    学习了，谢谢分享。

    0

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    2018-09-02 zdvfsadb

    学习了

    0

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