Objective
To characterize transforming growth factor beta1 (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 (PPI) for erectile dysfunction (ED) and divided into 2 groups: post-radical prostatectomy ED (RP-ED; n=57) or 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 (FN; 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 both RP-ED (p<0.05) and O-ED (p<0.05) groups compared to that of the CON group, and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3 and FN were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to PPI was related to increased expression of pSmad2 (p<0.05) and previous history of intracavernosal injection was related to increased expression of TGFβ1 (p<0.05) .
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.