title: FOXO1 delays skeletal muscle regeneration and suppresses myoblast proliferation.
abstract: Unloading stress, such as bed rest, inhibits the regenerative potential of skeletal muscles; however, the underlying mechanisms remain largely unknown. FOXO1 expression, which induces the upregulated expression of the cell cycle inhibitors p57 and Gadd45α, is known to be increased in the skeletal muscle under unloading conditions. However, there is no report addressing FOXO1-induced inhibition of myoblast proliferation. Therefore, we induced muscle injury by cardiotoxin in transgenic mice overexpressing FOXO1 in the skeletal muscle (FOXO1-Tg mice) and observed regeneration delay in skeletal muscle mass and cross-sectional area in FOXO1-Tg mice. Increased p57 and Gadd45α mRNA levels, and decreased proliferation capacity were observed in C2C12 myoblasts expressing a tamoxifen-inducible active form of FOXO1. These results suggest that decreased proliferation capacity of myoblasts by FOXO1 disrupts skeletal muscle regeneration under FOXO1-increased conditions, such as unloading.
authors.affiliation: a Graduate School of Life and Environmental Sciences , Kyoto Prefectural University , Kyoto , Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: a Graduate School of Life and Environmental Sciences , Kyoto Prefectural University , Kyoto , Japan.|b Japan Society for the Promotion of Science , Tokyo , Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Hatazawa
authors.affiliation: a Graduate School of Life and Environmental Sciences , Kyoto Prefectural University , Kyoto , Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Hirose
authors.affiliation: c Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
authors.affiliation: a Graduate School of Life and Environmental Sciences , Kyoto Prefectural University , Kyoto , Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D000071161:Forkhead Box Protein O1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D019417:Hindlimb Suspension; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D004179:Cobra Cardiotoxin Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D000071161:Forkhead Box Protein O1; D009687:Nuclear Proteins; C493965:Cdkn1c protein, mouse; C467200:Foxo1 protein, mouse; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins
keywords: FOXO1; cell proliferation; skeletal muscle