title: IGF-II-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α in myoblast cells involves PI3K/Akt/FoxO1 signaling pathway.
abstract: Insulin-like growth factor II (IGF-II) can stimulate myogenesis and is critically involved in skeletal muscle differentiation. The presence of negative regulators of this process, however, is not well explored. Here, we showed that in myoblast cells, IGF-II negatively regulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA expression, while constitutive expression of PGC-1α induced myoblast differentiation. These results suggest that the negative regulation of PGC-1α by IGF-II may act as a negative feedback mechanism in IGF-II-induced myogenic differentiation. Reporter assays demonstrated that IGF-II suppresses the basal PGC-1α promoter activity. Blocking the IGF-II signaling pathway increased the endogenous PGC-1α levels. In addition, pharmacological inhibition of PI3 kinase activity prevented the downregulation of PGC-1α but the activation of mTOR was not required for this process. Importantly, further analysis showed that forkhead transcription factor FoxO1 contributes to mediating the effects of IGF-II on PGC-1 promoter activity. These findings indicate that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.|University of Jinan Quancheng College, Jinan, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Obstetrics, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Qi
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
authors.forename: Yunzhang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Rong
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China. linglu@ouc.edu.cn.
authors.forename: Ling
authors.identifier: http://orcid.org/0000-0002-3336-7744
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D002460:Cell Line; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; C513121:IGF2 protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D007335:Insulin-Like Growth Factor II; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: FoxO1; IGF-II; Myogenesis; PGC-1α