Mammalian target of rapamycin complex 1 is involved in differentiation of regenerating myofibers in vivo.
This work was undertaken to provide further insight into the role of mammalian target of rapamycin complex 1 (mTORC1) in skeletal muscle regeneration, focusing on myofiber size recovery. Rats were treated or not with rapamycin, an mTORC1 inhibitor. Soleus muscles were then subjected to cryolesion and analyzed 1, 10, and 21 days later. A decrease in soleus myofiber cross-section area on post-cryolesion days 10 and 21 was accentuated by rapamycin, which was also effective in reducing protein synthesis in these freeze-injured muscles. The incidence of proliferating satellite cells during regeneration was unaltered by rapamycin, although immunolabeling for neonatal myosin heavy chain (MHC) was weaker in cryolesion+rapamycin muscles than in cryolesion-only muscles. In addition, the decline in tetanic contraction of freeze-injured muscles was accentuated by rapamycin. This study indicates that mTORC1 plays a key role in the recovery of muscle mass and the differentiation of regenerating myofibers, independently of necrosis and satellite cell proliferation mechanisms.
Miyabara
Elen H
EH
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Conte
Talita C
TC
Silva
Meiricris T
MT
Baptista
Igor L
IL
Bueno
Carlos
C
Fiamoncini
Jarlei
J
Lambertucci
Rafael H
RH
Serra
Carmen S
CS
Brum
Patricia C
PC
Pithon-Curi
Tania
T
Curi
Rui
R
Aoki
Marcelo S
MS
Oliveira
Antonio C
AC
Moriscot
Anselmo S
AS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D005615:Freezing; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009124:Muscle Proteins / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D009124:Muscle Proteins; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D018995:Myosin Heavy Chains; D020123:Sirolimus