Inhibition of TGF-β signaling pathway as a potential therapeutic strategy for Peyronie's diease and erectile dysfunction

초록

S12-5 Inhibition of TGF-βsignaling pathway as a potential therapeutic strategy for Peyronie’s disease and erectile dysfunction Ji-Kan Ryu and Jun-Kyu Suh National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea Transforming growth factor-β1 (TGF-β1) has been known to play a crucial role in the pathogenesis of Peyronie’s disease (PD) and erectile dysfunction (ED). PD is a fibrotic process of the tunica albuginea that is characterized by penile deformity and curvature from localized fibrotic plaque. Here, we demonstrate that ALK5 inhibitor blocked TGF-β1- induced phosphorylation of Smad2 and Smad3, and reduced production of extracellular matrix proteins in fibroblasts derived from human PD plaque. Moreover, ALK5 inhibitor induced significant regression of fibrotic plaque through reduced infiltration of inflammatory cells, reduced transnuclear expression of p-Smad2/p-Smad3, and reduced hydroxyproline content and restoration of elastin fibers in the fibrotic plaque of PD rats, which was accompanied by the correction of penile curvature. Adenovirus encoding Smad7 restored erectile function by reducing apoptosis of cavernous endothelial and smooth muscle cells in an animal model for ED induced by cavernous nerve injury. These findings suggest that pharmacologic inhibition of TGF-βsignaling pathway may represent a novel targeted approach to treating PD and ED. Supported by Basic Science Research Program through the NRF funded by MEST (2010-0023026).