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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Fibrinogen inhibits neurite outgrowth via β3 integrin-mediated phosphorylation of the EGF receptor
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Fibrinogen inhibits neurite outgrowth via β3 integrin-mediated phosphorylation of the EGF receptor

机译：纤维蛋白原通过β3整合素介导的EGF受体磷酸化抑制神经突生长

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摘要

Changes in the molecular and cellular composition of the CNS after injury or disease result in the formation of an inhibitory environment that inhibits the regeneration of adult mammalian CNS neurons. Although a dramatic change in the CNS environment after traumatic injury or disease is hemorrhage because of vascular rupture or leakage of the blood-brain barrier, the potential role for blood proteins in repair processes remains unknown. Here we show that the blood protein fibrinogen is an inhibitor of neurite outgrowth that is massively deposited in the spinal cord after injury. We show that fibrinogen acts as a ligand for β3 integrin and induces the transactivation of EGF receptor (EGFR) in neurons. Fibrinogen-mediated inhibition of neurite outgrowth is reversed by blocking either β3 integrin or phoshorylation of EGFR. Inhibition of Src family kinases that mediate the cross-talk between integrin and growth factor receptors rescue the fibrinogen-induced phosphorylation of EGFR. These results identify fibrinogen as the first blood-derived inhibitor of neurite outgrowth and suggest fibrinogen-induced EGFR transactivation on neuronal cells as a molecular link between vascular and neuronal damage in the CNS after injury.
机译：损伤或疾病后中枢神经系统分子和细胞组成的变化导致抑制环境的形成，该抑制环境抑制了成年哺乳动物中枢神经系统神经元的再生。尽管在外伤或疾病后中枢神经系统环境发生的巨大变化是由于血管破裂或血脑屏障的渗漏引起的出血，但血液蛋白在修复过程中的潜在作用仍然未知。在这里，我们显示血液蛋白纤维蛋白原是神经突增生的抑制剂，其在损伤后大量沉积在脊髓中。我们显示纤维蛋白原充当β3整合素的配体并诱导神经元中EGF受体（EGFR）的反式激活。通过阻断β3整合素或EGFR磷酸化作用，可以逆转纤维蛋白原对神经突生长的抑制作用。介导整联蛋白和生长因子受体之间的串扰的Src家族激酶的抑制作用挽救了纤维蛋白原诱导的EGFR磷酸化。这些结果确定纤维蛋白原是第一个源自血液的神经突生长抑制剂，并提示纤维蛋白原在神经元细胞上诱导的EGFR反式激活是损伤后中枢神经系统血管和神经元损伤之间的分子联系。

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