Abstract | PURPOSE: Transforming growth factor-β1 (TGF-β1) is the key fibrogenic cytokine associated with Peyronie's disease (PD). The aim of this study was to determine the antifibrotic effect of 3-((5-(6-Methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl) methyl)benzamide (IN-1130), a small-molecule inhibitor of the TGF-β type I receptor activin receptor-like kinase 5 (ALK5), in fibroblasts isolated from human PD plaque. MATERIALS AND METHODS: RESULTS: The treatment of fibroblasts with TGF-β1 significantly increased phosphorylation of Smad2 and Smad3 and induced translocation of Smad proteins from the cytoplasm to the nucleus. Pretreatment with IN-1130 substantially inhibited TGF-β1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins. The TGF-β1-induced production of extracellular matrix proteins was also significantly inhibited by treatment with IN-1130 and returned to basal levels. CONCLUSIONS: Overexpression of TGF-β and activation of Smad transcriptional factors are known to play a crucial role in the pathogenesis of PD. Thus, inhibition of the TGF-β signaling pathway by ALK5 inhibitor may represent a promising therapeutic strategy for treating PD.
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Authors | Jin Hyuk Jang, Ji Kan Ryu, Jun Kyu Suh |
Journal | Korean journal of urology
(Korean J Urol)
Vol. 53
Issue 1
Pg. 44-9
(Jan 2012)
ISSN: 2005-6745 [Electronic] Korea (South) |
PMID | 22323974
(Publication Type: Journal Article)
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