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.

Muscle & Nerve
|February 21, 2013
PubMed
Abstract

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.