MiR-135a-5p/SP1 Axis Regulates Spinal Astrocyte Proliferation and Migration

作者：Lin, Xin; Yang, Yang; Ji, Ye; Wang, Guangxi; Xu, Wenbo; Wang, Bo; Guo, Hangyu; Ren, Jiyu; Yan, Jinglong^*; Wang, Nanxiang^*

来源：Neuroscience, 2023, 515: 12-24.

DOI：10.1016/j.neuroscience.2023.01.038

• miR-135a-5p
• SP1
• astrocyte
• proliferation
• migration
• spinal cord injury

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) dur -ing SCI results in altered expression of downstream genes. Our previous study has revealed that miR-135a-5p reg-ulates 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.

• 单位
  中山大学; 哈尔滨医科大学