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Updated: May 14, 2026

Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice
Published on: November 3, 2013
Loss of SPARC in mouse skeletal muscle causes myofiber atrophy
Katsuyuki Nakamura1, Shin-Ichi Nakano, Takahiro Miyoshi
1Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Introduction:
The expression of secreted protein acidic and rich in cysteine (SPARC) in skeletal muscle decreases with age. Here, we examined the role of SPARC in skeletal muscle by reducing its expression.
Methods:
SPARC expression was suppressed by introducing short interfering RNA (siRNA) into mouse tibialis anterior muscle. Myofiber diameter, atrogin1, and muscle RING-finger protein 1 (MuRF1) expression, and tumor necrosis factor-α (TNFα) and transforming growth factor-β (TGFβ) signaling were then analyzed.
Results:
Reduced SPARC expression caused decreases in the diameter of myofibers, especially fast-type ones, accompanied by upregulation of atrogin1, but not MuRF1, at 10 days after siRNA transfection. The expression of TNFα and TGFβ and the phosphorylation status of p38 were not affected by SPARC knockdown, whereas Smad3 phosphorylation was increased at 2 days after siRNA transfection.
Conclusions:
The loss of SPARC not only upregulates atrogin1 expression but also enhances TGFβ signaling, which may in turn cause muscle atrophy.
Insights
Secreted protein acidic and rich in cysteine (SPARC) loss in skeletal muscle increases atrogin1 and enhances TGFβ signaling, potentially causing muscle atrophy. This study investigated SPARC
Area of Science:
- Muscle physiology
- Molecular biology
- Aging research
Background:
- Secreted protein acidic and rich in cysteine (SPARC) expression declines in skeletal muscle with age.
- Understanding SPARC's role in muscle health is crucial for age-related conditions.
Purpose of the Study:
- To investigate the functional role of SPARC in skeletal muscle.
- To determine the effects of reduced SPARC expression on muscle characteristics and signaling pathways.
Main Methods:
- SPARC expression was suppressed in mouse tibialis anterior muscle using short interfering RNA (siRNA).
- Analyzed myofiber diameter, atrogin1, MuRF1 expression, and TNFα and TGFβ signaling pathways.
Main Results:
- Reduced SPARC expression led to decreased myofiber diameter, particularly in fast-twitch fibers.
- Atrogin1 expression was upregulated, while MuRF1 remained unaffected.
- Increased Smad3 phosphorylation indicated enhanced TGFβ signaling, without affecting TNFα or p38 pathways.
Conclusions:
- Loss of SPARC upregulates atrogin1 and enhances TGFβ signaling.
- These molecular changes suggest a mechanism by which SPARC deficiency contributes to skeletal muscle atrophy.
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