Time-dependent expression of myostatin RNA transcript and protein in gastrocnemius muscle of mice after sciatic nerve resection
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Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice
Published on: November 3, 2013
Chenxin Shao1, Mei Liu, Xin Wu
1Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, JS 226001 People's Republic of China.
Abstract:
Myostatin, a member of the transforming growth factor-beta (TGF-beta) superfamily, has been identified as a negative regulator of skeletal muscle mass. To provide more data on the role of myostatin in denervation-induced muscle atrophy, we examined the time-dependent changes in myostatin mRNA and protein as well as Smad2 and phospho-Smad2 protein levels in the denervated gastrocnemius muscle of mice after sciatic neurectomy, using quantitative real-time RT-PCR and Western blotting, respectively. We conducted morphometric analyses to measure the wet weight ratio of the denervated muscle (the operated side/contralateral nonoperated side) and the cross-sectional area of muscle fibers, and observed the morphology of denervated muscle. The experimental results showed that in the early stage of denervation, the levels of myostatin mRNA and protein in the denervated gastrocnemius muscle increased instantly, reaching a peak at day 3 and day 7 after sciatic neurectomy, respectively, when compared with the normal values. In addition, the phospho-Smad2 protein was observed to have a similar expression profile to that of the myostatin mRNA. The present study perhaps opens a new window into myostatin modulation in muscle atrophy due to denervation.
Insights
Myostatin levels increase rapidly in denervated muscles, peaking early after sciatic nerve injury. This suggests myostatin plays a key role in muscle atrophy following denervation.
Area of Science:
- Muscle physiology and molecular biology
- Skeletal muscle atrophy research
- Transforming growth factor-beta (TGF-beta) superfamily signaling
Background:
- Myostatin is a known negative regulator of skeletal muscle mass.
- Understanding myostatin's role in denervation-induced muscle atrophy is crucial for therapeutic development.
Purpose of the Study:
- To investigate the time-dependent changes in myostatin expression and signaling pathways in response to denervation.
- To correlate myostatin dynamics with morphological changes in atrophied muscle.
Main Methods:
- Sciatic neurectomy in mice to induce denervation.
- Quantitative real-time RT-PCR for myostatin mRNA analysis.
- Western blotting for myostatin, Smad2, and phospho-Smad2 protein quantification.
- Morphometric analyses of muscle weight and fiber cross-sectional area.
Main Results:
- Myostatin mRNA and protein levels significantly increased in denervated gastrocnemius muscle.
- Myostatin expression peaked at 3 days (mRNA) and 7 days (protein) post-neurectomy.
- Phospho-Smad2 protein levels mirrored the myostatin mRNA expression profile.
- Muscle atrophy was confirmed through decreased wet weight ratio and fiber area.
Conclusions:
- Myostatin expression is rapidly upregulated following denervation, indicating its involvement in muscle atrophy.
- The Smad2 signaling pathway appears to be activated concurrently with myostatin upregulation.
- These findings highlight myostatin as a potential therapeutic target for mitigating denervation-induced muscle loss.
