Department of Veterinary Medical Science, University of Bologna, Ozzano dell'Emilia, 40064 Bologna, Italy.
Fondazione IRET, Ozzano dell'Emilia, 40064 Bologna, Italy.
Int J Mol Sci. 2021 Feb 9;22(4):1744. doi: 10.3390/ijms22041744.
The involvement of the extracellular matrix (ECM) in lesion evolution and functional outcome is well recognized in spinal cord injury. Most attention has been dedicated to the "core" area of the lesion and scar formation, while only scattered reports consider ECM modification based on the temporal evolution and the segments adjacent to the lesion. In this study, we investigated the expression profile of 100 genes encoding for ECM proteins at 1, 8 and 45 days post-injury, in the spinal cord segments rostral and caudal to the lesion and in the scar segment, in a rat model. During both the active lesion phases and the lesion stabilization, we observed an asymmetric gene expression induced by the injury, with a higher regulation in the rostral segment of genes involved in ECM remodeling, adhesion and cell migration. Using bioinformatic approaches, the metalloproteases inhibitor and the hyaluronan receptor emerged as the hub genes at all post-lesion times. Results from the bioinformatic gene expression analysis were then confirmed at protein level by tissue analysis and by cell culture using primary astrocytes. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury.
细胞外基质（ECM）在脊髓损伤中的病变演变和功能结果中起着重要作用。大多数研究都集中在病变的“核心”区域和疤痕形成上，而只有少数报道考虑了基于时间演变和损伤相邻节段的 ECM 修饰。在这项研究中，我们在大鼠模型中，在损伤后 1、8 和 45 天，在损伤上下脊髓节段和疤痕节段，研究了 100 个编码 ECM 蛋白的基因的表达谱。在活跃的病变阶段和病变稳定阶段，我们观察到损伤诱导的不对称基因表达，与 ECM 重塑、黏附和细胞迁移相关的基因在损伤的近端节段的调节更高。通过生物信息学方法，金属蛋白酶抑制剂 和透明质酸受体 在所有损伤后时间点均成为枢纽基因。组织分析和使用原代星形胶质细胞进行细胞培养的生物信息学基因表达分析结果证实了这一点。这些结果表明，在脊髓损伤中，ECM 调节也发生在损伤区域之外。
