Increased cavernous expression of transforming growth factor-β1 and activation of the smad signaling pathway affects erectile dysfunction in men with spinal cord injury

Tae Young Shin, Ji Kan Ryu, Hai Rong Jin, Shuguang Piao, Munkhbayar Tumurbaatar, Guo Nan Yin, Sun Hwa Shin, Mi Hye Kwon, Kang Moon Song, Zheng Huan Fang, Jee Young Han, Woo Jean Kim, Jun Kyu Suh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)1454-1462
Number of pages9
JournalJournal of Sexual Medicine
Volume8
Issue number5
DOIs
StatePublished - May 2011

Bibliographical note

Funding Information:
This study was supported by grant no. R0A-2007-000-20018-0 (Jun-Kyu Suh) from the Korea Science and Engineering Foundation (KOSEF) funded by the Korea government (Ministry of Education, Science, and Technology, MEST). The authors thank Jennifer Holmes for help in preparing the article.

Keywords

  • Erectile Dysfunction
  • Fibrosis
  • Smad
  • Spinal Cord Injury
  • Transforming Growth Factor-Beta

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