title: Dedifferentiation of adult human myoblasts induced by ciliary neurotrophic factor in vitro.
abstract: Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular effects within the nervous system. However, recent studies indicate that its receptor can be highly expressed in denervated skeletal muscle. Here, we investigated the direct effect of CNTF on skeletal myoblasts of adult human. Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts at a clonal level to dedifferentiate into multipotent progenitor cells--they not only could proliferate for over 20 passages with the expression absence of myogenic specific factors Myf5 and MyoD, but they were also capable of differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle cells, and adipocytes. These "progenitor cells" retained their myogenic memory and were capable of redifferentiating into myotubes. Furthermore, CNTF could activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway, was able to abolish the effects of CNTF on both myoblast fate and MRF expression. Our results demonstrate the myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway.
authors.affiliation: Department of Neurophysiology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Zebin
authors.initials: Z
authors.lastname: Mao
authors.forename: Shuhong
authors.initials: S
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: David T
authors.initials: DT
authors.lastname: Yew
authors.forename: Pawel M
authors.initials: PM
authors.lastname: Kindler
authors.forename: Linsong
authors.initials: L
authors.lastname: Li
authors.forename: Qihua
authors.initials: Q
authors.lastname: He
authors.forename: Lingjia
authors.initials: L
authors.lastname: Qian
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D041681:NIH 3T3 Cells; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors
chemical_list: D020934:Ciliary Neurotrophic Factor; D004791:Enzyme Inhibitors; D005419:Flavonoids; C497417:MYF5 protein, human; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one