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.
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Elen H
EH
Miyabara
Talita C
TC
Conte
Meiricris T
MT
Silva
Igor L
IL
Baptista
Carlos
C
Bueno
Jarlei
J
Fiamoncini
Rafael H
RH
Lambertucci
Carmen S
CS
Serra
Patricia C
PC
Brum
Tania
T
Pithon-Curi
Rui
R
Curi
Marcelo S
MS
Aoki
Antonio C
AC
Oliveira
Anselmo S
AS
Moriscot
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