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


CONCLUSIONS
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.
Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Surgery, Division of Urology, Sao Paulo Federal University, Sao Paulo, Brazil; CAPES Foundation, Ministry of Education of Brazil, Brasilia, Brazil.
Marcelo R
MR
Cabrini
Sena F
SF
Sezen
Gwen
G
Lagoda
Robert L
RL
Segal
Zhaoyong
Z
Feng
Cassio
C
Andreoni
Arthur L
AL
Burnett
D000368:Aged; D007172:Erectile Dysfunction / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010413:Penis / Q000378:metabolism*; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D051896:Smad Proteins, Receptor-Regulated; D053773:Transforming Growth Factor beta1