Department of Orthopaedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, PR China.
Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, PR China.
Neuroscience. 2023 Apr 1;515:12-24. doi: 10.1016/j.neuroscience.2023.01.038. Epub 2023 Feb 9.
Following spinal cord injury (SCI), astrocyte activation and proliferation result in the development of glial scars, which impede axonal growth and neurological recovery. Dysregulation of microRNAs (miRNAs) during SCI results in altered expression of downstream genes. Our previous study has revealed that miR-135a-5p regulates neuronal apoptosis and axonal growth by targeting specificity protein 1 (SP1). This study attempted to investigate whether the miR-135a-5p/SP1 axis has regulatory effect on astrocytes. Herein, lipopolysaccharide (LPS) reduced miR-135a-5p expression in astrocytes. miR-135a-5p overexpression in astrocytes resulted in a decrease in CyclinD1, MMP9, GFAP, and vimentin proteins, and thus attenuated LPS-induced proliferation and migration of astrocytes. Moreover, miR-135a-5p overexpression decreased astrocyte size and the total quantity of cell protrusions, suggesting a role for miR-135a-5p in regulating astrocyte morphology. SP1 silencing also decreased astrocyte proliferation and migration by LPS. SP1 silencing could significantly reverse the promoting effect of miR-135a-5p inhibition on astrocyte proliferation and migration. In summary, the miR-135a-5p/SP1 axis regulates astrocyte proliferation and migration after SCI. This finding benefits for the development of novel ways in treating SCI effectively.
脊髓损伤（SCI）后，星形胶质细胞的激活和增殖导致胶质瘢痕的形成，从而阻碍轴突的生长和神经功能的恢复。SCI 期间 microRNAs（miRNAs）的失调导致下游基因表达的改变。我们之前的研究表明，miR-135a-5p 通过靶向特异性蛋白 1（SP1）调节神经元凋亡和轴突生长。本研究试图探讨 miR-135a-5p/SP1 轴是否对星形胶质细胞有调节作用。在此，脂多糖（LPS）降低了星形胶质细胞中的 miR-135a-5p 表达。星形胶质细胞中 miR-135a-5p 的过表达导致 CyclinD1、MMP9、GFAP 和波形蛋白蛋白的减少，从而减弱了 LPS 诱导的星形胶质细胞增殖和迁移。此外，miR-135a-5p 的过表达降低了星形胶质细胞的大小和细胞突起的总数量，表明 miR-135a-5p 在调节星形胶质细胞形态中起作用。SP1 沉默也通过 LPS 降低了星形胶质细胞的增殖和迁移。SP1 沉默可以显著逆转 miR-135a-5p 抑制对星形胶质细胞增殖和迁移的促进作用。综上所述，miR-135a-5p/SP1 轴调节 SCI 后星形胶质细胞的增殖和迁移。这一发现有利于开发有效治疗 SCI 的新方法。
