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Updated: Dec 24, 2025
A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury
Published on: September 13, 2018
Overexpression of miRNA-433-5p protects acute spinal cord injury through activating MAPK1
1Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. zhouchanglin119@163.com.
Objective:
The aim of this study was to clarify the role of microRNA-433-5p (miRNA-433-5p) in influencing pathological lesions following acute spinal cord injury (SCI) by targeting mitogen-activated protein kinase 1 (MAPK1).
Patients And Methods:
SCI model was successfully established in mice by performing hitting injury procedures. Serum levels of miRNA-433-5p and MAPK1 in SCI patients and mice were determined. Grip strengths of both forelimbs in SCI mice and controls were determined. Dual-Luciferase reporter gene assay was applied to verify the binding relation between miRNA-433-5p and MAPK1. After overexpression of miRNA-433-5p and MAPK1 in vivo, the grip strength changes in SCI mice were assessed. Furthermore, the protein level of inflammatory factor iNOS in 293T cells influenced by miRNA-433-5p and MAPK1 was detected by Western blot.
Results:
MiRNA-433-5p was significantly downregulated in the serum of SCI patients and mice, whereas MAPK1 was up-regulated. Grip strengths of SCI mice were significantly lower than those of controls at different postoperative time points. However, this could be markedly reversed by the in vivo overexpression of miRNA-433-5p. Western blot indicated that the protein level of iNOS was remarkably downregulated in 293T cells overexpressing miRNA-433-5p. MAPK1 was confirmed as the target of miRNA-433-5p, whose expression level was negatively regulated by miRNA-433-5p. Importantly, MAPK1 partially reversed the protective role of miRNA-433-5p in grip strength of SCI mice and inflammatory response at post-SCI.
Conclusions:
Overexpression of miRNA-433-5p protects SCI-induced motor dysfunction and inflammatory response by targeting MAPK1.
Insights
MicroRNA-433-5p (miRNA-433-5p) protects against spinal cord injury (SCI) by targeting MAPK1. Restoring miRNA-433-5p levels improves motor function and reduces inflammation after SCI.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Spinal cord injury (SCI) leads to significant motor dysfunction and pathological lesions.
- The role of specific microRNAs in SCI pathogenesis remains incompletely understood.
- Mitogen-activated protein kinase 1 (MAPK1) is implicated in inflammatory responses following injury.
Purpose of the Study:
- To investigate the role of microRNA-433-5p (miRNA-433-5p) in acute spinal cord injury (SCI).
- To determine if miRNA-433-5p influences pathological lesions by targeting mitogen-activated protein kinase 1 (MAPK1).
Main Methods:
- Established a mouse model of SCI via hitting injury.
- Quantified serum levels of miRNA-433-5p and MAPK1 in SCI patients and mice.
- Assessed grip strength in SCI mice post-intervention.
- Utilized Dual-Luciferase reporter gene assay to confirm miRNA-433-5p and MAPK1 interaction.
- Detected iNOS protein levels via Western blot in response to miRNA-433-5p and MAPK1 manipulation.
Main Results:
- Serum miRNA-433-5p was downregulated, while MAPK1 was upregulated in SCI patients and mice.
- SCI mice exhibited significantly reduced grip strength, which was reversed by miRNA-433-5p overexpression.
- MAPK1 was confirmed as a direct target of miRNA-433-5p, with its expression negatively regulated.
- Overexpression of miRNA-433-5p reduced iNOS protein levels, indicating an anti-inflammatory effect.
Conclusions:
- miRNA-433-5p plays a protective role in acute SCI.
- Overexpression of miRNA-433-5p mitigates motor dysfunction and inflammatory responses post-SCI.
- The therapeutic effect of miRNA-433-5p is mediated through its targeting of MAPK1.
