Laboratory of Molecular Endocrinology, Federal State Budgetary Organization National Cardiology Research Center Ministry of Health of the Russian Federation, Institute of Experimental Cardiology, 3d Cherepkovskaya st. 15а, Moscow, 121552, Russia; Faculty of Medicine, Lomonosov Moscow State University, Lomonosovsky av. 27-1, Moscow, 119991, Russia.
Laboratory of Molecular Endocrinology, Federal State Budgetary Organization National Cardiology Research Center Ministry of Health of the Russian Federation, Institute of Experimental Cardiology, 3d Cherepkovskaya st. 15а, Moscow, 121552, Russia; Faculty of Medicine, Lomonosov Moscow State University, Lomonosovsky av. 27-1, Moscow, 119991, Russia.
Biomed Pharmacother. 2020 May;125:110008. doi: 10.1016/j.biopha.2020.110008. Epub 2020 Feb 28.
Urokinase receptor (uPAR) promotes extracellular matrix proteolysis, regulates adhesion and cell migration, transduces intracellular signals through interactions with the lateral partners. The expression of uPAR and urokinase (uPA) is significantly upregulated in peripheral nerves after injury, however, little is known about uPAR function in nerve regeneration or the molecular mechanisms involved. The purpose of this study is to investigate the role of uPAR in nerve regeneration after traumatic injury of n. Peroneus communis in uPA-/-, uPAR-/- or control mice (WT) and in neuritogenesis in an in vitro Neuro 2A cell model.
Electrophysiological analysis indicates that nerve recovery is significantly impaired in uPAR-/- mice, but not in uPA-/- mice. These data correlate with the reduced amount of NF200-positive axons in regenerating nerves from uPAR-/- mice compared to uPA-/- or control mice. There is an increase in uPAR expression and remarkable colocalization of uPAR with α5 and β1 integrin in uPA-/- mice in recovering nerves, pointing to a potential link between uPAR and its lateral partner α5β1-integrin. Using an in vitro model of neuritogenesis and α325 blocking peptide, which abrogates uPAR-α5β1 interaction in Neuro 2A cells but has no effect on their function, we have further confirmed the significance of uPAR-α5β1 interaction.
Taken together, we report evidence pointing to an important role of uPAR, rather than uPA, in peripheral nerve recovery and neuritogenesis.
尿激酶受体（uPAR）促进细胞外基质的蛋白水解，调节黏附和细胞迁移，并通过与侧向伙伴的相互作用转导细胞内信号。在损伤后，周围神经中 uPAR 和尿激酶（uPA）的表达显著上调，然而，关于 uPAR 在神经再生中的功能或涉及的分子机制知之甚少。本研究的目的是研究 uPAR 在创伤性损伤 n. 腓总神经后的神经再生中的作用。Peroneus communis 在 uPA-/-、uPAR-/-或对照小鼠（WT）和体外 Neuro 2A 细胞模型中的神经突生成中的作用。
电生理分析表明，uPAR-/-小鼠的神经恢复明显受损，但 uPA-/-小鼠则没有。这些数据与 uPAR-/-小鼠再生神经中 NF200 阳性轴突的数量减少相关，与 uPA-/-或对照小鼠相比。在恢复神经中，uPAR 的表达增加，并且 uPAR 与 α5 和 β1 整合素明显共定位，这表明 uPAR 与其侧向伙伴 α5β1-整合素之间存在潜在联系。使用体外神经突生成模型和 α325 阻断肽，该肽在 Neuro 2A 细胞中阻断 uPAR-α5β1 相互作用，但对其功能没有影响，我们进一步证实了 uPAR-α5β1 相互作用的重要性。
总之，我们报告了指向 uPAR 而不是 uPA 在周围神经恢复和神经突生成中的重要作用的证据。
