title: mTOR is necessary for proper satellite cell activity and skeletal muscle regeneration.
abstract: The serine/threonine kinase mammalian target of rapamycin (mTOR) is a key regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive deletion of Mtor gene results in embryonic lethality, the function of mTOR in muscle stem cells (satellite cells) and skeletal muscle regeneration remains to be determined. In this study, we established a satellite cell specific Mtor conditional knockout (cKO) mouse model by crossing Pax7(CreER) and Mtor(flox/flox) mice. Skeletal muscle regeneration after injury was severely compromised in the absence of Mtor, indicated by increased number of necrotic myofibers infiltrated by Evans blue dye, and reduced number and size of regenerated myofibers in the Mtor cKO mice compared to wild type (WT) littermates. To dissect the cellular mechanism, we analyzed satellite cell-derived primary myoblasts grown on single myofibers or adhered to culture plates. The Mtor cKO myoblasts exhibited defective proliferation and differentiation kinetics when compared to myoblasts derived from WT littermates. At the mRNA and protein levels, the Mtor cKO myoblasts expressed lower levels of key myogenic determinant genes Pax7, Myf5, Myod, Myog than did the WT myoblasts. These results suggest that mTOR is essential for satellite cell function and skeletal muscle regeneration through controlling the expression of myogenic genes.
authors.affiliation: Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Tizhong
authors.initials: T
authors.lastname: Shan
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; College of Animal Science and Technology, Guangxi University, Nanning 530004, China.
authors.forename: Qinyang
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Changyan
authors.initials: C
authors.lastname: Deng
authors.affiliation: Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: zhengrong@mail.hzau.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: skuang@purdue.edu.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000293:injuries / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D012333:RNA, Messenger; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: Muscle regeneration; Satellite cells; Skeletal muscle; mTOR