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  4. Recombinant myostatin reduces highly expressed microRNAs in differentiating C2C12 cells

Recombinant myostatin reduces highly expressed microRNAs in differentiating C2C12 cells

Biochemistry and Biophysics Reports, 2017 · DOI: http://dx.doi.org/10.1016/j.bbrep.2017.01.003 · Published: January 17, 2017

PhysiologyGenetics

Simple Explanation

Myostatin, a protein secreted by skeletal muscle, is a negative regulator of muscle growth. This study investigates how myostatin affects microRNAs (miRNAs) in muscle cells. miRNAs are small molecules that regulate gene expression. The researchers treated C2C12 muscle cells with recombinant myostatin and an ALK4/5/7 inhibitor (SB431542) to see how these treatments altered miRNA expression during cell differentiation. They found that myostatin reduced the expression of some myomiRs (muscle-specific miRNAs) while the inhibitor generally increased their expression. These findings suggest that myostatin can repress myomiR expression in differentiating muscle cells and that inhibiting Smad signaling (a pathway involved in myostatin's action) can lead to significant changes in highly expressed miRNAs.

Study Duration
1 and 3 days
Participants
Mouse C2C12 myoblasts
Evidence Level
Not specified

Key Findings

  • 1
    Myostatin (1 µg/ml) reduced the expression of miR-1 and miR-133a at 1 day post-differentiation induction but not at 3 days.
  • 2
    The ALK4/5/7 inhibitor SB431542 increased the expression of miRs 1, 133a, 133b, 206 and 486 at 1 day when administered alone or in combination with low dose myostatin.
  • 3
    Myostatin and SB431542 altered MyoD levels at 1 day, suggesting potential effects on cell differentiation, but these agents did not affect MyoD levels at 3 days.

Research Summary

This study investigates the effects of myostatin and an ALK4/5/7 inhibitor (SB431542) on miRNA expression in differentiating C2C12 myoblasts to understand the regulation of muscle-specific and highly expressed miRNAs. The results indicate that myostatin represses the expression of certain myomiRs in differentiating C2C12 cells, while inhibition of Smad signaling with SB431542 leads to significant changes in highly expressed miRNAs. The study also found that the timing of treatment after inducing differentiation influenced the response to myostatin or the ALK4/5/7 inhibitor, suggesting the cellular context is important for myostatin and ALK/4/5/7 signaling.

Practical Implications

Understanding Muscle Atrophy

The findings provide insights into the mechanisms by which myostatin regulates muscle growth and atrophy through miRNA modulation, which could be relevant for conditions like spinal cord injury and frailty.

Therapeutic Targets

Identifying specific miRNAs regulated by myostatin and ALK4/5/7 signaling could lead to the development of targeted therapies to promote muscle growth and prevent muscle wasting.

Optimizing Treatment Strategies

The study highlights the importance of considering the stage of cell differentiation when designing therapeutic interventions targeting myostatin signaling, as the effects on miRNA expression may vary depending on the timing of treatment.

Study Limitations

  • 1
    The study was conducted in vitro using C2C12 myoblasts, which may not fully represent the complexity of muscle regulation in vivo.
  • 2
    The specific mechanisms by which myostatin and ALK4/5/7 signaling regulate miRNA expression were not fully elucidated.
  • 3
    The study focused on a selected set of miRNAs, and other miRNAs may also be involved in the regulation of muscle growth and atrophy by myostatin.

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