Loss of SPARC in mouse skeletal muscle causes myofiber atrophy

Abstract

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.

Keywords: SPARC; Smad3; TGFβ; atrogin1; myofiber atrophy.