The Signature of MicroRNA Dysregulation in Muscle Paralyzed by Spinal Cord Injury Includes Downregulation of MicroRNAs that Target Myostatin Signaling

PLoS ONE, 2016 · DOI: 10.1371/journal.pone.0166189 · Published: December 1, 2016

Spinal Cord Injury Genetics Musculoskeletal Medicine

Simple Explanation

Spinal cord injury (SCI) leads to muscle wasting, reduced strength, and a shift in muscle fiber type. This study explores the role of small RNA molecules called microRNAs (miRs) in these muscle changes after SCI. The researchers compared miRs in paralyzed muscle of rats with SCI to those without SCI. They found that certain miRs, like miR-23a, 145, and 206, were reduced in muscle after SCI. These miRs normally target genes involved in muscle growth and insulin sensitivity. The study suggests that their reduction may contribute to muscle loss and insulin resistance in paralyzed muscle after SCI.

Study Duration

56 days

Participants

Male Wistar-Hannover rats

Evidence Level

Not specified

Key Findings

1
miRs 23a, 23b, 27b, 145, and 206, were downregulated in skeletal muscle 56 days after SCI.
2
miR-145, a miR not previously implicated in the function of skeletal muscle, was found to be localized to skeletal muscle fibers.
3
Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes.

Research Summary

This study investigated microRNA (miR) expression profiles in paralyzed gastrocnemius muscle of rats after spinal cord injury (SCI) compared to sham-operated rats to understand the mechanisms behind muscle deterioration. The findings indicate dysregulation of several highly expressed miRs in skeletal muscle after SCI, particularly reduced expression of miR-23a, 145, and 206, suggesting their involvement in muscle mass alteration and insulin responsiveness. The study also identified that miR-145 is localized to skeletal muscle fibers and confirmed that miR-145 interacts with a seed sequence in the 3’ UTR of Cited2 mRNA, although Cited2 protein levels remained similar between Sham and SCI groups.

Practical Implications

Therapeutic targets

miRs 23a, 145 and 206 may represent therapeutic targets for treating muscle atrophy and insulin resistance after SCI.

Understading of muscle atrophy

The identification of specific miRs and their target pathways contributes to a better understanding of the molecular mechanisms driving muscle atrophy following SCI.

Clinical Translation

These findings may provide a foundation for developing targeted interventions to preserve muscle mass and function in individuals with SCI.

Study Limitations

1
The study was performed on rats, and the results may not be directly applicable to humans.
2
The study focused on a single time point (56 days after SCI), and the temporal dynamics of miR expression changes may be more complex.
3
The functional significance of some of the observed miR changes remains to be fully elucidated.

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