Angiopoietin-1 induces neurite outgrowth of PC12 cells in a Tie2-independent, beta1-integrin-dependent manner.
Angiopoietin-1 induces neurite outgrowth of PC12 cells in a Tie2-independent, beta1-integrin-dependent manner.
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DOI：
10.1016/j.neures.2009.04.007
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发表时间：
2009-08
影响因子：
2.9
通讯作者：
Ward NL
中科院分区：
文献类型：
--
作者：
Chen X;Fu W;Tung CE;Ward NL
脑内血管生成素（Angiopoietin，Ang）1的过表达可导致血管生成增加和神经元树突形态改变。我们假设Ang 1直接作用于神经元，诱导神经突生长。我们用Ang 1刺激PC 12细胞，并观察到与神经生长因子（NGF）相当的生长水平。Western blotting和RT-PCR结果显示，Ang 1受体和Tie 2均缺失，β1整合素存在。在β1-整合素下游，Ang 1刺激导致粘着斑激酶（FAK）磷酸化增加约2.6倍，而丝裂原活化蛋白激酶（MAPK）和c-Jun N-末端激酶（JNK）的活化无变化。相反，NGF刺激对FAK磷酸化没有影响，但导致MAPK和JNK磷酸化增加约3.1和约2倍。在β1-整合素和FAK的功能抑制后，Ang 1而不是NGF介导的生长减弱，Wortmannin抑制由两者介导的神经突生长。我们的研究结果表明，Ang 1以Tie 2非依赖性、β1-integrin-FAK-PI 3 K-Akt依赖性的方式诱导PC 12细胞中的神经突起生长，并且NGF和Ang 1通过两种独立的信号传导机制介导神经突起生长。
Overexpression of Angiopoietin (Ang) 1 in the brain results in increased vascularization and altered neuronal dendrite configuration. We hypothesized that Ang1 acts directly on neurons inducing neurite outgrowth. We stimulated PC12 cells with Ang1 and observed outgrowth levels comparable to nerve growth factor (NGF). Western blotting and RT-PCR demonstrated the absence of the Ang1 receptor, Tie2 and the presence of β1-integrin. Downstream of β1-integrin, Ang1 stimulation led to a ~2.6 fold increase in focal adhesion kinase (FAK) phosphorylation and no change in activation of mitogen-activated protein kinase (MAPK) nor c-Jun N-terminal kinase (JNK). Conversely, NGF stimulation had no effect on FAK phosphorylation but lead to a ~3.1 and ~2 fold increase in phosphorylation of MAPK and JNK. Ang1, but not NGF-mediated outgrowth was attenuated following functional inhibition of β1-integrin and FAK, and Wortmannin inhibited neurite outgrowth mediated by both. Our results suggest that Ang1 induces neurite outgrowth in PC12 cells in a Tie2-independent, β1-integrin-FAK-PI3K-Akt dependent manner and that NGF and Ang1 mediate neurite outgrowth via two independent signaling mechanisms.
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