title: The effects of hepatocyte growth factor and insulin-like growth factor-1 on the myogenic differentiation of satellite cells in human urethral rhabdosphincter.
abstract: OBJECTIVE
  To examine the effects of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) on the myogenic differentiation of human urethral rhabdosphincter (RS) satellite cells.
  
  
  METHODS
  Human RS was obtained from patients undergoing radical prostatectomy for prostate cancer. Selectively cultured RS satellite cells, transfected with temperature sensitive simian virus-40 T antigen (ts-SV40 Tag) to extend their lifespan, were cultured at 33 degrees C, and then incubated at 39 degrees C to induce myogenic differentiation. Varying concentrations of HGF and IGF-1 were added to the differentiation medium. Inactivation of SV40 Tag and evaluations of myogenic differentiation were examined by immunocytochemistry, western blotting and real-time RT-PCR.
  
  
  RESULTS
  At 39 degrees C, ts-SV40 Tag-transfected RS satellite cells slowly proliferated, fused to form multinucleated myotubes, and expressed myosin heavy chain (MHC) in association with the temperature-dependent inactivation of SV40 Tag. IGF-1 significantly accelerated the MHC expression in a dose-dependent fashion through activation of the PI3-kinase pathway. Conversely, HGF did not promote MHC expression due a reduction in phosphorylation of both the MAP-kinase and the PI3-kinase pathways, a pattern of response different than the response of proliferating RS satellite cells to HGF.
  
  
  CONCLUSIONS
  HGF did not induce myogenic differentiation of RS satellite cells. Conversely, IGF-1 promoted myogenic differentiation of RS satellite cells via the PI3-K pathway likewise proliferating RS satellite cells. These findings may be useful for developing novel techniques for regenerating the human RS to treat urinary incontinence.
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sumino
authors.forename: Mari
authors.initials: M
authors.lastname: Hanada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hirata
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sato
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology*; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects* / Q000502:physiology*; D014521:Urethra / Q000166:cytology*
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D017228:Hepatocyte Growth Factor