• Kang Moon Song, Jae-Seung Chung, Min Ji Choi, Hai-Rong Jin, Guo Nan Yin, Mi-Hye Kwon, Jin-Mi Park, Woo Jean Kim, Sang-Jin Lee, Seong-Jin Kim, Ji-Kan Ryu, and Jun-Kyu Suh.
• National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
• J Sex Med. 2014 Jan 1; 11 (1): 51-63.

IntroductionMen with erectile dysfunction (ED) respond poorly to oral phosphodiesterase-5 inhibitors following radical prostatectomy. Recent studies have reported that up-regulation of transforming growth factor-β1 (TGF-β1) and activation of the Smad signaling pathway play important roles in cavernous fibrosis and in the deterioration of erectile function in a mouse model of cavernous nerve injury (CNI) and in patients with spinal cord injury. The mothers against decapentaplegic homolog 7 (Smad7) is known to inhibit the phosphorylation of Smad2 and Smad3.AimTo investigate the effectiveness of adenoviruses encoding Smad7 gene (Ad-Smad7) on erectile function in a mouse model of CNI.MethodsTwelve-week-old C57BL/6J mice were used and distributed into 7 groups: sham operation group, untreated CNI group, and CNI groups receiving a single intracavernous injection of adenovirus encoding LacZ (1 × 10(8) virus particles [vp]/20 μL) or adenovirus encoding Smad7 (Ad-Smad7; 1 × 10(7), 1 × 10(8), 2 × 10(8), or 1 × 10(9) vp/20 μL).Main Outcome MeasuresTwo weeks after bilateral cavernous nerve crushing and treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis.ResultsThe highest erectile response was noted in CNI mice treated with Ad-Smad7 at a dose of 1 × 10(8)  vp, which reached up to 82-85% of sham control values. Local delivery of Ad-Smad7 significantly decreased endothelial cell apoptosis and the production of extracellular matrix proteins, including plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV, and induced endothelial nitric oxide synthase phosphorylation in the corpus cavernosum tissue of CNI mice.ConclusionThe adenovirus-mediated gene transfer of Smad7 successfully restored erectile function by enhancing endothelial cell function and through antifibrotic effects. These findings suggest that inhibition of the TGF-β signaling pathway by use of Smad7 may represent a promising therapeutic strategy for ED induced by radical prostatectomy.© 2013 International Society for Sexual Medicine.

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