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Increased Cavernous Expression of Transforming Growth Factor-β1 and Activation of the Smad Signaling Pathway Affects Erectile Dysfunction in Men with Spinal Cord Injury

Authors

  • Tae-Young Shin MD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Ji-Kan Ryu MD, PhD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Hai-Rong Jin MD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Shuguang Piao MD, PhD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Munkhbayar Tumurbaatar MD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Guo Nan Yin MS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Sun Hwa Shin BS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Mi-Hye Kwon BS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Kang-Moon Song BS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Zheng-Huan Fang BS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Jee-Young Han MD, PhD,

    1. Department of Pathology, Inha University School of Medicine, Incheon, Korea
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  • Woo Jean Kim PhD,

    Corresponding author
    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Jun-Kyu Suh MD, PhD

    Corresponding author
    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Tae-Young Shin and Ji-Kan Ryu contributed equally to this study.

Jun-Kyu Suh, MD, PhD, National Research Laboratory of Regenerative 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; or

Woo Jean Kim, PhD, National Research Laboratory of Regenerative 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: 82-32-890-2466; Fax: 82-32-890-2462; E-mail: pangjean@korea.com

ABSTRACT

Introduction.  Transforming growth factor-β1 (TGF-β1) is implicated in bladder fibrosis after spinal cord injury (SCI) and in the fibrosis in the corpus cavernosum tissue after cavernous nerve injury.

Aim.  We investigated the differential expression of TGF-β1 and the Smad transcription factor, the key molecule for the initiation of TGF-β-mediated fibrosis, in cavernous tissue from SCI patients.

Methods.  After obtaining informed consent and approval from the patients and our institutional review board, we enrolled 5 patients with psychogenic erectile dysfunction (ED) (mean age 36.8 years; range 20–50 years) and 10 patients with neurogenic ED from SCI (mean age 38.8 years; range 18–50 years). Cavernous tissues were obtained by percutaneous biopsy and stained with Masson trichrome, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL), or antibodies to TGF-β1 and phospho-Smad2.

Main Outcome Measures.  Semi-quantitative analysis of TGF-β1 and phospho-Smad2 was performed, and the numbers of apoptotic cells were counted. We also quantified the cavernous collagen area with the use of an image analyzer system.

Results.  The expression of TGF-β1 and phospho-Smad2 protein was significantly higher in the SCI group than in the psychogenic group. The TUNEL assay revealed a higher apoptotic index in the SCI group than in the psychogenic group. Higher TGF-β1 and phospho-Smad2 expression and more apoptotic cells were noted mainly in endothelial cells, smooth muscle cells, and fibroblasts of the SCI group. Double labeling of cavernous tissue with TUNEL and antibody to phospho-Smad2 revealed that most TUNEL-positive cells showed immunoreactivity to phospho-Smad2 staining. Cavernous collagen content was significantly greater in the SCI group than in the psychogenic group.

Conclusion.  Upregulation of TGF-β1 and activation of the Smad signaling pathway may play important roles in SCI-induced cavernous fibrosis and deterioration of erectile function, which warrants early pharmacological intervention to protect erectile tissue from irreversible damage. Shin T-Y, Ryu J-K, Jin H-R, Piao S, Tumurbaatar M, Yin GN, Shin SH, Kwon M-H, Song K-M, Fang Z-H, Han J-Y, Kim WJ, and Suh J-K. Increased cavernous expression of transforming growth factor-β1 and activation of the smad signaling pathway affects erectile dysfunction in men with spinal cord injury. J Sex Med 2011;8:1454–1462.

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