Exogenous hepatocyte growth factor inhibits myoblast differentiation by inducing myf5 expression and suppressing myoD expression in an organ culture system of embryonic mouse tongue.
We examined the effects of exogenous hepatocyte growth factor (HGF) on the differentiation and proliferation of tongue myoblasts by using an organ culture system of tongue obtained from mouse embryos at embryonic day (E) 13. Exogenous HGF induced reductions in the quantities of muscle creatine kinase and myogenin mRNAs and in the number of fast myosin heavy chain-positive myoblasts and myotubes, suggesting that HGF suppressed the differentiation of myoblasts in the cultured E13 tongues. Exogenous HGF induced no significant changes in the percentage of proliferating cell nuclear antigen (PCNA)-positive cell nuclei to total cell nuclei (labeling index) in the muscle portion of the cultured E13 tongue, suggesting that HGF did not affect the proliferation of myoblasts. Exogenous HGF induced the expression of myf5 mRNA but inhibited the expression of myoD mRNA. Since mouse tongue myoblasts are reported to complete proliferation by E13, it appears that exogenous HGF arrests myoblasts in the cell cycle and does not allow them to enter the differentiation process. This is achieved by controlling the expression of myf5 and myoD mRNAs, thus inhibiting the differentiation of tongue myoblasts.
Yamane
Akira
A
Department of Pharmacology, Tsurumi University School of Dental Medicine, Yokohama, Japan. GAH03667@nifty.ne.jp
Amano
Osamu
O
Urushiyama
Toki
T
Nagata
Junji
J
Akutsu
Satonari
S
Fukui
Tadayoshi
T
Diekwisch
Thomas G H
TG
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D003402:Creatine Kinase / Q000187:drug effects; D004268:DNA-Binding Proteins; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009124:Muscle Proteins / Q000187:drug effects*; D017570:MyoD Protein / Q000187:drug effects*; D032446:Myoblasts / Q000187:drug effects*; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000187:drug effects; D009924:Organ Culture Techniques; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014059:Tongue / Q000187:drug effects / Q000196:embryology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000187:drug effects*
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D003402:Creatine Kinase; D018995:Myosin Heavy Chains