MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury

Int. J. Biol. Sci., 2018 · DOI: 10.7150/ijbs.24074 · Published: January 15, 2018

Simple Explanation

After a spinal cord injury (SCI), the body forms scars that block nerves from regrowing. This study looks at how a small RNA molecule, miR-21-5p, affects this scarring process. The study found that miR-21-5p, along with a protein called TGF-β1, are both increased in the injured area after SCI. TGF-β1 causes cells called fibroblasts to become more active in forming scar tissue. By reducing the amount of miR-21-5p in mice with SCI, the researchers saw improved recovery of movement. This suggests that miR-21-5p could be a target for treatments to reduce scarring and improve recovery after SCI.

Study Duration

14 days

Participants

84 mice

Evidence Level

Not specified

Key Findings

1
TGF-β1 enhances miR-21-5p expression in primary spinal fibroblasts, and regulates the expression of fibrosis-related genes.
2
miR-21-5p knockdown in a mouse model significantly improved motor functional recovery after spinal cord injury.
3
Smad7 is identified as a target gene of miR-21-5p, suggesting a potential mechanism for the role of miR-21-5p in spinal fibrosis through regulating Smad7 expression.

Research Summary

This study investigates the role of miR-21-5p in fibrotic scar formation after spinal cord injury (SCI). The findings demonstrate that TGF-β1 enhances miR-21-5p expression in spinal fibroblasts, promoting pro-fibrogenic activity, while miR-21-5p knockdown attenuates this activity. Knockdown of miR-21-5p in a mouse model significantly improved motor functional recovery after SCI, suggesting miR-21-5p as a potential therapeutic target.

Practical Implications

Therapeutic Target

miR-21-5p is a potential therapeutic target in the treatment of fibrotic scar formation after SCI.

Drug Development

Development of drugs targeting miR-21-5p could attenuate fibrotic scar formation and improve functional outcomes after SCI.

Clinical Strategies

Targeting miR-21-5p represents a novel strategy to promote axon regeneration and neurological recovery in SCI patients.

Study Limitations

1
The study is limited to a mouse model of SCI, and results may not be directly translatable to humans.
2
The precise mechanisms by which miR-21-5p functions in spinal neuron cells and neuroglial cells remain unclear.
3
The amplifying circuit between miR-21-5p and the TGF-β pathway may not be the only factor causing poor prognosis after SCI.

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