Pan Bin, Yu Hongwei, Park John, Yu Yanhui Peter, Luo Z David, Hogan Quinn H
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
J Neurosci Res. 2015 Mar;93(3):443-53. doi: 10.1002/jnr.23498. Epub 2014 Oct 18.
Thrombospondin-4 (TSP4) belongs to a family of large, oligomeric extracellular matrix glycoproteins that mediate interactions between cells and interactions of cells with underlying matrix components. Recent evidence shows that TSP4 might contribute to the generation of neuropathic pain. However, there has been no systematic examination of TSP4 expression in the dorsal root ganglia (DRG) after injury. This study, therefore, investigates whether TSP4 protein level is changed in DRG after injury following spinal nerve ligation (SNL) and spared nerve injury in rats by performing Western blotting, immunohistochemistry, and immunocytochemistry. After nerve ligation, TSP4 protein level is upregulated in the axotomized somata of the fifth lumbar (L5) DRG. There is substantial additional TSP4 in the nonneuronal compartment of the L5 DRG that does not costain for markers of satellite glia, microglia, or Schwann cells and appears to be in the interstitial space. Evidence of intracellular overexpression of TSP4 persists in neurons dissociated from the L5 DRG after SNL. These findings indicate that, following peripheral nerve injury, TSP4 protein expression is elevated in the cytoplasm of axotomized sensory neurons and in the surrounding interstitial space.
血小板反应蛋白-4(TSP4)属于一类大型寡聚细胞外基质糖蛋白家族,可介导细胞间相互作用以及细胞与潜在基质成分间的相互作用。最近的证据表明,TSP4可能与神经性疼痛的产生有关。然而,尚未对损伤后背根神经节(DRG)中TSP4的表达进行系统研究。因此,本研究通过蛋白质免疫印迹法、免疫组织化学和免疫细胞化学方法,研究大鼠脊髓神经结扎(SNL)和保留神经损伤后DRG中TSP4蛋白水平是否发生变化。神经结扎后,第五腰段(L5)DRG轴突切断的胞体中TSP4蛋白水平上调。L5 DRG的非神经元区室中有大量额外的TSP4,其与卫星神经胶质细胞、小胶质细胞或雪旺细胞的标志物无共染色,似乎存在于间质空间。SNL后从L5 DRG分离的神经元中持续存在TSP4细胞内过表达的证据。这些发现表明,周围神经损伤后,轴突切断的感觉神经元细胞质和周围间质空间中TSP4蛋白表达升高。