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Published on: July 20, 2011
Downregulation of miRNA-127-5p aggravates spinal cord injury through activating MAPK1
1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China. sdfeydqr@163.com.
Objective:
To uncover the role of microRNA-127-5p (miRNA-127-5p) in aggravating motor dysfunction following spinal cord injury (SCI) by regulating the mitogen-activated protein kinase 1 (MAPK1) level.
Materials And Methods:
In vivo SCI model in mice was established by constructing spinal cord hitting injury. Mice were classified into sham group, SCI group, SCI+miRNA-127-5p mimics group, and SCI+miRNA-127-5p mimics+MAPK1 group, respectively. Grip strengths of mouse pair forepaws, right forepaw, and left forepaw at different time points were determined. Expression levels of miRNA-127-5p and MAPK1 in mice of each group at post-SCI were detected. Potential binding sites in promoter regions of miRNA-127-5p and MAPK1 were predicted by bioinformatics and further confirmed by Dual-Luciferase reporter gene assay and Western blot.
Results:
Grip strengths of SCI mice were much lower than those in sham group at different time points after SCI procedures. MiRNA-127-5p was markedly downregulated on the postoperative 3rd day in SCI group, and its level time-dependently decreased since after. In vivo overexpression of miRNA-127-5p in SCI mice improved their grip strengths from the postoperative 7th day. MAPK1 was the direct target of miRNA-127-5p. Transfection of miRNA-127-5p mimics downregulated protein level of MAPK1 in 293T cells. Overexpression of MAPK1 abolished the protective effect of miRNA-127-5p on motor function recovery following SCI.
Conclusions:
Downregulation of miRNA-127-5p aggravates SCI-induced motor dysfunction through negatively regulating MAPK1 level.
Insights
MicroRNA-127-5p (miRNA-127-5p) downregulation worsens spinal cord injury (SCI) motor deficits. Restoring miRNA-127-5p levels improves grip strength by targeting mitogen-activated protein kinase 1 (MAPK1).
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Spinal cord injury (SCI) often leads to persistent motor dysfunction.
- MicroRNAs (miRNAs) play crucial roles in post-injury recovery.
- The specific role of microRNA-127-5p (miRNA-127-5p) in SCI pathophysiology remains unclear.
Purpose of the Study:
- To investigate the role of miRNA-127-5p in motor dysfunction after SCI.
- To determine if miRNA-127-5p regulates mitogen-activated protein kinase 1 (MAPK1) levels.
- To elucidate the therapeutic potential of modulating miRNA-127-5p in SCI.
Main Methods:
- An in vivo mouse model of spinal cord hitting injury was established.
- Mice were grouped into sham, SCI, SCI + miRNA-127-5p mimics, and SCI + miRNA-127-5p mimics + MAPK1.
- Grip strength, miRNA-127-5p and MAPK1 expression levels were assessed; molecular interactions were confirmed via bioinformatics, dual-luciferase reporter assays, and Western blot.
Main Results:
- SCI mice exhibited significantly reduced grip strength compared to the sham group.
- miRNA-127-5p was downregulated post-SCI, with levels decreasing over time.
- Overexpression of miRNA-127-5p improved motor function and reduced MAPK1 protein levels; MAPK1 overexpression negated these benefits.
Conclusions:
- Downregulation of miRNA-127-5p exacerbates motor dysfunction following spinal cord injury.
- miRNA-127-5p exerts a protective effect by negatively regulating MAPK1.
- Targeting miRNA-127-5p represents a potential therapeutic strategy for SCI.
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