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.
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.
Authors: Vanessa L Brayman; Thomas Taetzsch; MacKenzie Miko; Shreyaska Dahal; W Christopher Risher; Gregorio Valdez Journal: Neurosci Lett Date: 2021-01-22 Impact factor: 3.046
Authors: Kyoung-Jin Oh; Da Som Lee; Won Kon Kim; Baek Soo Han; Sang Chul Lee; Kwang-Hee Bae Journal: Int J Mol Sci Date: 2016-12-22 Impact factor: 5.923
Authors: Rachel Munk; Jennifer L Martindale; Xiaoling Yang; Jen-Hao Yang; Ioannis Grammatikakis; Clara Di Germanio; Sarah J Mitchell; Rafael de Cabo; Elin Lehrmann; Yongqing Zhang; Kevin G Becker; Vered Raz; Myriam Gorospe; Kotb Abdelmohsen; Amaresh C Panda Journal: PLoS One Date: 2019-03-29 Impact factor: 3.240