Growth mechanism of satellite cells in human urethral rhabdosphincter.
OBJECTIVE
To examine the presence of satellite cells in human urethral rhabdosphincter (RS) and to clarify the growth mechanism of these cells.


METHODS
Human RS was obtained from patients undergoing radical prostatectomy for prostate cancer. Primary cells were selectively cultured by magnetic affinity cell sorting (MACS) using an anti-neural cell adhesion molecule (NCAM) antibody. Selectively cultured cells, transfected with simian virus-40 T antigen to extend their lifespan, were used for the following experiments: (1) determination of the effects of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (b-FGF); (2) clarification of the signal transduction pathways used by these growth factors; and (3) examination of the autocrine actions in these cells.


RESULTS
Selectively cultured cells expressed striated muscle markers and could differentiate into myotubes. HGF and IGF-1 stimulated the growth of these cells in a dose-dependent fashion. Regarding signal transduction, HGF phosphorylated ERK1/2 for 120 min while only transiently modifying Akt. In contrast, IGF-1 phosphorylated Akt but not ERK1/2. Furthermore, these cells produced transcripts and proteins for both HGF and IGF-1, and anti-HGF and anti-IGF-1 antibodies suppressed cell proliferation.


CONCLUSIONS
Satellite cells are present in human RS. The proliferation of these cells is primarily enhanced through both the endogenous and exogenous actions of HGF and IGF-I via ERK1/2 and Akt. These findings may be useful in the development of a novel technique for the regeneration of human RS to treat urinary incontinence.
Sumino
Yasuhiro
Y
Department of Oncological Science (Urology), Oita University Faculty of Medicine, Oita, Japan.
Hirata
Yuji
Y
Department of Oncological Science (Urology), Oita University Faculty of Medicine, Oita, Japan.
Sato
Fuminori
F
Department of Oncological Science (Urology), Oita University Faculty of Medicine, Oita, Japan.
Mimata
Hiromitsu
H
Department of Oncological Science (Urology), Oita University Faculty of Medicine, Oita, Japan.
D000368:Aged; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D009500:Neutralization Tests; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D014162:Transfection; D014521:Urethra / Q000166:cytology* / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016222:Fibroblast Growth Factor 2; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one