title: Loss of SPARC in mouse skeletal muscle causes myofiber atrophy.
abstract: BACKGROUND
  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.
authors: Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors: Katsuyuki
authors: K
authors: Nakamura
authors: Shin-Ichi
authors: S
authors: Nakano
authors: Takahiro
authors: T
authors: Miyoshi
authors: Keitaro
authors: K
authors: Yamanouchi
authors: Masugi
authors: M
authors: Nishihara
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015676:Osteonectin / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D009124:Muscle Proteins; D015676:Osteonectin; D034741:RNA, Small Interfering; C578250:SPARC protein, mouse; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: SPARC; Smad3; TGFβ; atrogin1; myofiber atrophy