title: PGC-1α over-expression suppresses the skeletal muscle atrophy and myofiber-type composition during hindlimb unloading.
abstract: Disuse leads to severe muscle atrophy and a slow-to-fast myofiber-type transition. PGC-1α (Peroxisome proliferator-activated receptor γ coactivator 1α) is documented to play an important role in muscle atrophy and slow-twitch myofiber determination. Transcription of atrophy-related Atrogin-1 by FoxO3 can be reduced by PGC-1α. While Smad3 augments FoxO3-induced Atrogin-1 and MuRF1 promoter activity. So PGC-1α, as a transcription co-activator, may regulate hindlimb unloading (HU)-induced myofiber-type transition and muscle atrophy through Smad3. Our results showed that transgenic PGC-1α mice resisted HU-induced muscle loss, atrophy-related genes expression, and slow-to-fast myofiber-type transition. Furthermore, over-expression of PGC-1α resisted the increase in pSmad3 during muscle atrophy in vivo and in vitro. And, PGC-1α over-expression inhibited the expression of atrogenes via suppressing the phosphorylation of Smad3 in vitro. Thus, PGC-1α is effective in regulating myofiber-type transition during HU, and it alleviates skeletal muscle atrophy partially through suppressing the activation of Smad3.
authors.affiliation: a Department of Neurobiology , School of Basic Medical Sciences, Capital Medical University , Beijing , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: b National Key Laboratory of Human Factors Engineering , China Astronaut Research and Training Center , Beijing , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: c State Key Laboratory of Space Medicine Fundamentals and Application , China Astronaut Research and Training Center , Beijing , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: c State Key Laboratory of Space Medicine Fundamentals and Application , China Astronaut Research and Training Center , Beijing , China.
authors.forename: Hongju
authors.initials: H
authors.lastname: Liu
authors.affiliation: c State Key Laboratory of Space Medicine Fundamentals and Application , China Astronaut Research and Training Center , Beijing , China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: d State Key Laboratory of Pharmaceutical Biotechnology , School of Life Sciences, Nanjing University , Nanjing , China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: a Department of Neurobiology , School of Basic Medical Sciences, Capital Medical University , Beijing , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: b National Key Laboratory of Human Factors Engineering , China Astronaut Research and Training Center , Beijing , China.|c State Key Laboratory of Space Medicine Fundamentals and Application , China Astronaut Research and Training Center , Beijing , China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D019417:Hindlimb Suspension / Q000009:adverse effects*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D000070584:Tripartite Motif Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: PGC-1α; Smad3; hindlimb unloading; myofiber type; skeletal muscle atrophy