title: FGF13 regulates proliferation and differentiation of skeletal muscle by down-regulating Spry1.
abstract: OBJECTIVE
  Generally, the secretory forms of FGF are known to regulate cell proliferation, differentiation and morphogenesis by binding to the extracellular domain of cell surface receptors. Intracellular FGFs (FGF11-14) are expressed principally in the nervous system. FGF13 is a microtubule-stabilizing protein that regulates neuronal polarization and migration. Previous studies have reported high expression of FGF13 in cultures of single muscle fibres. However, functions of FGF13 in muscle development have not been explored.
  
  
  METHODS
  Real-time RT-PCR was performed to detect expression of FGF13 during C2C12 muscle cell proliferation and differentiation. To further understand the role of FGF13, its effects on proliferation and differentiation were examined by western blot analyses of cells transfected with FGF13 siRNA or FGF13 expression plasmids, or treated with chemical MEK inhibitors. Effects of FGF13 on related signalling pathways in C2C12 cell proliferation and differentiation were determined.
  
  
  RESULTS
  FGF13 inhibited C2C12 cell proliferation by up-regulating p27 mRNA level and by down-regulating Cyclin E protein expression, during cell proliferation. Additionally, FGF13 down-regulated Spry1 protein expression, activating the ERK1/2 pathway by phosphorylation and leading to C2C12 cell differentiation inhibition. Consequently, FGF13 seemed to function as a repressor of myoblast differentiation via the ERK1/2 pathway. Although FGF13 inhibited Spry1 regardless of cell proliferation or differentiation, its pathway activation occurred only during the stage of myoblast differentiation.
  
  
  CONCLUSIONS
  FGF13 inhibited C2C12 cell proliferation and differentiation by down-regulating Spry1. These findings indicate that FGF13 played a negative regulatory role in skeletal muscle development.
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.|School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, Shaanxi, 723000, China.
authors.forename: Hongzhao
authors.initials: H
authors.lastname: Lu
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Xine
authors.initials: X
authors.lastname: Shi
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Guofang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Chengchuang
authors.initials: C
authors.lastname: Song
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Qiangling
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Gongshe
authors.initials: G
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019927:Cyclin E; D008565:Membrane Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C425468:Spry1 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3