Get access

Effectiveness of Intracavernous Delivery of Adenovirus Encoding Smad7 Gene on Erectile Function in a Mouse Model of Cavernous Nerve Injury

Authors

  • Kang Moon Song MS,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    Search for more papers by this author
    • These authors contributed equally to this study.
  • Jae-Seung Chung MD, PhD,

    1. Department of Urology, Inje University College of Medicine, Busan, Korea
    Search for more papers by this author
    • These authors contributed equally to this study.
  • Min Ji Choi MS,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    Search for more papers by this author
  • Hai-Rong Jin MD, PhD,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    2. Department of Urology, Yuhuangding Hospital, Yantai, Shandong, China
    Search for more papers by this author
  • Guo Nan Yin PhD,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    Search for more papers by this author
  • Mi-Hye Kwon MS,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    Search for more papers by this author
  • Jin-Mi Park MS,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    Search for more papers by this author
  • Woo Jean Kim PhD,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    Search for more papers by this author
  • Sang-Jin Lee PhD,

    1. Genitourinary Cancer Branch, National Cancer Center Research Institute, Goyang, Gyeonggi-Do, Korea
    Search for more papers by this author
  • Seong-Jin Kim PhD,

    1. CHA Cancer Institute, CHA University, Seoul, Korea
    Search for more papers by this author
  • Ji-Kan Ryu MD, PhD,

    Corresponding author
    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    • Corresponding Authors: Jun-Kyu Suh, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd ST, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr and Ji-Kan Ryu, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd ST, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3505; Fax: 82-32-890-3099; E-mail: rjk0929@inha.ac.kr

    Search for more papers by this author
  • Jun-Kyu Suh MD, PhD

    Corresponding author
    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    • Corresponding Authors: Jun-Kyu Suh, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd ST, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr and Ji-Kan Ryu, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd ST, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3505; Fax: 82-32-890-3099; E-mail: rjk0929@inha.ac.kr

    Search for more papers by this author

Abstract

Introduction

Men 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.

Aim

To investigate the effectiveness of adenoviruses encoding Smad7 gene (Ad-Smad7) on erectile function in a mouse model of CNI.

Methods

Twelve-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 × 108 virus particles [vp]/20 μL) or adenovirus encoding Smad7 (Ad-Smad7; 1 × 107, 1 × 108, 2 × 108, or 1 × 109 vp/20 μL).

Main Outcome Measures

Two 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.

Results

The highest erectile response was noted in CNI mice treated with Ad-Smad7 at a dose of 1 × 108 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.

Conclusion

The 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. Song KM, Chung J-S, Choi MJ, Jin H-R, Yin GN, Kwon M-H, Park J-M, Kim WJ, Lee S-J, Kim S-J, Ryu J-K, and Suh J-K. Effectiveness of intracavernous delivery of adenovirus encoding Smad7 gene on erectile function in a mouse model of cavernous nerve injury. J Sex Med 2014;11:51–63.

Ancillary