Low dose of IGF-I increases cell size of skeletal muscle satellite cells via Akt/S6K signaling pathway.
The objective of this study was to investigate the effect of insulin growth factor-I (IGF-I) on the size of pig skeletal muscle satellite cells (SCs). Using microarray, real-time RT-PCR, radioimmunoassay analysis and western blot, we first showed that supplementation of low-dose of IGF-I in culture medium resulted in enlarged cell size of Lantang SCs, only Akt and S6K were up-regulated at both the mRNA and protein levels among almost all of the mTOR pathway key genes, but had no effect on cell number. To elucidate the signaling mechanisms responsible for regulating cell size under low-dose of IGF-I treatment, we blocked Akt and S6K activity with the specific inhibitors MK2206 and PF4708671, respectively. Both inhibitors caused a decrease in cell size. In addition, MK2206 lowered the protein level of p-Akt (Ser473), p-S6K (Thr389), and p-rpS6 (Ser235/236), whereas PF4708671 lowered the protein level of p-S6K (Thr389) and p-rpS6 (Ser235/236). However, low dose of IGF-I didn't affect the protein level of p-mTOR (Ser2448) and p-mTOR (Ser2481). When both inhibitors were applied simultaneously, the effect was the same as that of the Akt inhibition alone. Taken together, we report for the first time that low-dose of IGF-I treatment increases cell size via Akt/S6K signaling pathway.
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry/Guangdong Provincial Key Laboratory of Agro-Animal Genomics, Guangzhou, Guangdong province, China.
Chun-qi
CQ
Gao
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry/Guangdong Provincial Key Laboratory of Agro-Animal Genomics, Guangzhou, Guangdong province, China.|Guizhou Agricultural Vocational College, Guiyang, Guizhou, China.
Rui
R
Zhi
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry/Guangdong Provincial Key Laboratory of Agro-Animal Genomics, Guangzhou, Guangdong province, China.|College of Science and Engineering, Guangxi Open University, Nanning, Guangxi, China.
Zhou
Z
Yang
Davis Heart & Lung Research Institute, Wexner Medical Center at the Ohio State University, Columbus, Ohio.
Hai-chang
HC
Li
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry/Guangdong Provincial Key Laboratory of Agro-Animal Genomics, Guangzhou, Guangdong province, China.
Hui-chao
HC
Yan
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry/Guangdong Provincial Key Laboratory of Agro-Animal Genomics, Guangzhou, Guangdong province, China.
Xiu-qi
XQ
Wang
D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine
D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; C548887:MK 2206; C552719:PF-4708671; D010879:Piperazines; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa
AKT; CELL SIZE; IGF-I; S6K; SATELLITE CELLS; mTOR