Dedifferentiation of adult human myoblasts induced by ciliary neurotrophic factor in vitro.
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.
Chen
Xiaoping
X
Department of Neurophysiology, Institute of Basic Medical Sciences, Beijing 100850, China.
Mao
Zebin
Z
Liu
Shuhong
S
Liu
Hong
H
Wang
Xuan
X
Wu
Haitao
H
Wu
Yan
Y
Zhao
Tong
T
Fan
Wenhong
W
Li
Yong
Y
Yew
David T
DT
Kindler
Pawel M
PM
Li
Linsong
L
He
Qihua
Q
Qian
Lingjia
L
Wang
Xiaomin
X
Fan
Ming
M
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
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