Myostatin inhibits proliferation of human urethral rhabdosphincter satellite cells

• Published in: International journal of urology Vol. 20; no. 5; pp. 522 - 529
• Main Authors: Akita, Yasuyuki, Sumino, Yasuhiro, Mori, Ken-ichi, Nomura, Takeo, Sato, Fuminori, Mimata, Hiromitsu
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.05.2013
• Subjects: Autocrine Communication; Cell Cycle Checkpoints - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Drug Evaluation, Preclinical; Humans; myostatin; Myostatin - pharmacology; Myostatin - therapeutic use; satellite cells; Signal Transduction - drug effects; urethra; Urethra - drug effects; urinary incontinence; Urinary Incontinence, Stress - drug therapy; urinary sphincter
• ISSN: 0919-8172; 1442-2042; 1442-2042
• DOI: 10.1111/j.1442-2042.2012.03186.x

Objectives Myostatin, a member of the transforming growth factor‐β superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. Methods Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti‐neural cell adhesion molecule antibody. The cells were transfected with simian virus‐40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real‐time reverse transcription polymerase chain reaction and immunoneutralization using an anti‐myostatin antibody was also evaluated. Results Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. Conclusions Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.