title: Role of increased penile expression of transforming growth factor-beta1 and activation of the Smad signaling pathway in erectile dysfunction in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  It has been suggested that transforming growth factor-beta1 (TGF-beta1) plays an important role in the pathogenesis of diabetes-induced erectile dysfunction.
  
  
  OBJECTIVE
  To investigate the expression and activity of Smad transcriptional factors, the key molecules for the initiation of TGF-beta-mediated fibrosis, in the penis of streptozotocin (STZ)-induced diabetic rats.
  
  
  METHODS
  Fifty-two 8-week-old Sprague-Dawley rats were used and divided into control and diabetic groups. Diabetes was induced by an intravenous injection of STZ.
  
  
  METHODS
  Eight weeks later, erectile function was measured by electrical stimulation of the cavernous nerve (N = 12 per group). The penis was harvested and stained with Masson trichrome or antibody to TGF-beta1, phospho-Smad2 (P-Smad2), smooth muscle alpha-actin, and factor VIII (N = 12 per group). Penis specimens from a separate group of animals were used for TGF-beta1 enzyme-linked immunosorbent assay (ELISA), P-Smad2/Smad2, phospho-Smad3 (P-Smad3)/Smad3, fibronectin, collagen I, and collagen IV western blot, or hydroxyproline determination.
  
  
  RESULTS
  Erectile function was significantly reduced in diabetic rats compared with that in controls. The expression of TGF-beta1, P-Smad2, and P-Smad3 protein evaluated by ELISA or western blot was higher in diabetic rats than in controls. Compared with that in control rats, P-Smad2 expression was higher mainly in smooth muscle cells and fibroblasts of diabetic rats, whereas no significant differences were noted in endothelial cells or in the dorsal nerve bundle. Cavernous smooth muscle and endothelial cell contents were lower in diabetic rats than in controls. Cavernous fibronectin, collagen IV, and hydroxyproline content was significantly higher in diabetic rats than in controls.
  
  
  CONCLUSIONS
  Upregulation of TGF-beta1 and activation of the Smad signaling pathway in the penis of diabetic rats might play important roles in diabetes-induced structural changes and deterioration of erectile function.
authors.affiliation: Department of Urology and Laboratory of Regenerative Sexual Medicine, Inha University School of Medicine, Incheon, Korea.
authors.forename: Lu Wei
authors.initials: LW
authors.lastname: Zhang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Piao
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Hwa-Yean
authors.initials: HY
authors.lastname: Shin
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jin
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Han
authors.forename: Seok Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Mizuko
authors.initials: M
authors.lastname: Mamura
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D007172:Erectile Dysfunction / Q000097:blood / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D008297:Male; D010413:Penis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1