Fibrotic protein expression profiles in penile tissue of patients with erectile dysfunction

Abstract

Objective: To characterize transforming growth factor beta 1 (TGFβ1) and related signaling pathway proteins in a large cohort of human penile tissue (HPT) samples.

Methods: HPT was collected from patients undergoing penile prosthesis implantation for erectile dysfunction (ED) and divided into the following 2 groups: postradical prostatectomy ED (RP-ED; n = 57) and organic ED (O-ED; n = 30). HPT from patients undergoing partial penectomy without ED was used as controls (CON; n = 6). Western blot analysis was performed to investigate the protein expressions of TGFβ1, thrombospondin 1 (TSP1; an activator of TGFβ1), fibronectin (an extracellular matrix glycoprotein induced by TGFβ1), and a family of transcriptional factors activated by TGFβ1 (Smad2, phospho-Smad2-serine-465/467 [pSmad2], Smad3, phospho-Smad3-serine-423/425 [pSmad3]).

Results: Expressions of TGFβ1 and TSP1 were significantly higher in RP-ED (P <.05) and O-ED (P <.05) groups compared with that of the CON group and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3, and fibronectin were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to penile prosthesis implantation was related to increased expression of pSmad2 (P <.05), and previous history of intracavernosal injection was related to increased expression of TGFβ1 (P <.05).

Conclusion: Our results demonstrate that TSP1- and TGFβ1-dependent fibrotic changes occur in penile tissue in patients with ED regardless of etiology. The unchanged expression of the Smad transcriptional factors may be reconciled by a Smad-independent downstream signaling pathway transmitting TGFβ1 signals.

Figure 1

Changes in TSP1 (A) and TGFβ1 (B) protein expressions. In both RP-ED and OED groups, expressions of TSP1 and TGFβ1 were significantly increased compared to CON group. ** p<0.01 vs CON. Top panels: representative immunoblots; bottom panel: densitometry data; bars represent means ± SD.

Figure 2

Subgroup analyses of the fibrotic protein expressions within the RP-ED group. The expression of TGFβ1 (A) was significantly increased in patients who reported a past history of ICI therapy [(+) ICI], compared to patients who did not [(−) ICI] * p<0.05 vs (−) ICI. The expression of pSmad2 (B) was significantly increased among patients who had a longer time (> 2 yrs) from RP to PPI than patients whose time since RP was shorter (<2 yrs). * p<0.05 vs >2 yrs. Top panels: representative immunoblots; bottom panel: densitometry data; bars represent means ± SD.