Development of Regeneration Therapy of External Urethral Sphincter based on the Regulation of Cytokine Signaling Pathway

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Fragility of urethral rhabdosphincter is one of the causes for urinary stress incontinence following prostatectomy and in the elderly. To develop new treatment modality of urinary incontinence by regeneration of urethral rhabdosphincter, human satellite cells of urethral rhabdosphincter were separated and cultured to explore the effects of variety of cytokines on them and the signal transduction.TNF-αdose-dependently suppressed the growth of satellite cells of human urethral rhabdosphincter and induced apoptosis in part, and anti- TNF-αdrugs inhibited these effects. Myostatin, skeletal muscle-specific growth inhibiting factor, was expressed on mRNA and protein levels in satellite cells of human urethral rhabdosphincter. Myostatin suppressed their growth dose-dependently, and its inhibitor, Follistatin, reversed its inhibitory effect.Regeneration of human urethral rhabdosphincter may be possible with anti-TNF-αdrugs and Myostatin inhibitors and prove a novel therapeutic modality for urinary incontinence.