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

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.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

Spinal cord injury (SCI) leads to glial scar formation, inhibiting axonal growth and neurological recovery. The miR-135a-5p/SP1 axis regulates astrocyte proliferation and migration, providing a potential target for effective SCI treatment.