Pompili Elena, Fabrizi Cinzia, Somma Francesca, Correani Virginia, Maras Bruno, Schininà Maria Eugenia, Ciraci Viviana, Artico Marco, Fornai Francesco, Fumagalli Lorenzo
Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
Mol Cell Neurosci. 2017 Mar;79:23-33. doi: 10.1016/j.mcn.2017.01.001. Epub 2017 Jan 4.
Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR.
蛋白酶激活受体-1（PAR1）是一类四个G蛋白偶联受体家族的典型成员，可响应细胞外蛋白酶发出信号。在周围神经系统中，PARs的表达和/或作用仍研究不足。在大鼠背根神经节中发现了高PAR1 mRNA表达，并且坐骨神经横断后PAR1 mRNA的信号强度增加。在坐骨神经中，据报道在郎飞结的非致密施万细胞髓鞘微绒毛水平存在功能性PAR1受体。施万细胞是周围神经系统神经胶质细胞的主要群体，它们使轴突髓鞘化，在轴突再生和髓鞘再生过程中起重要作用。本研究旨在确定PAR1的激活是否会影响施万细胞的神经营养特性。我们的结果表明，PAR1的刺激可增强施万细胞促进神经再生的能力。事实上，用特异性PAR1激活肽（PAR1 AP）刺激的施万细胞培养物获得的条件培养基相对于未处理的施万细胞的培养基显示出增强的神经保护和神经营养特性。对未处理和PAR1 AP处理的施万细胞中分泌蛋白的蛋白质组学分析，使我们能够鉴定出两个样品中差异表达的因子。其中一些因子（如巨噬细胞迁移抑制因子、基质金属蛋白酶-2、核心蛋白聚糖、多功能蛋白聚糖4、补体C1r亚成分、具有G结构域和FHA结构域的血管生成因子1）在PAR1 AP处理后似乎受到转录调控，这通过RT-PCR得以证明。
