Alterations in the transforming growth factor (TGF)-beta pathway as a potential factor in the pathogenesis of Peyronie's disease.
OBJECTIVE
The development of fibrotic diseases is associated with alterations in the transforming growth factor beta (TGF-beta) pathway. We have investigated the expression and activity of Smad transcription factors of the TGF-beta pathway in primary tunical fibroblasts derived from patients with Peyronie's disease and from controls.


METHODS
Primary fibroblasts were established from biopsies obtained from plaques of 16 patients with Peyronie's disease or the tunica albuginea of 8 control patients. The expression and activity of Smad transcription factors in control and TGF-beta-stimulated primary fibroblasts were investigated at the RNA and protein level by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence.


RESULTS
RNA expression levels of Smad3 and Smad4 were significantly increased in fibroblasts from patients with Peyronie's disease. When stimulated with TGF-beta1, fibroblasts showed rapid nuclear translocation of Smad2/3, as soon as 15 min after stimulation. This effect was more pronounced and exhibited an earlier onset in fibroblasts from patients with Peyronie's disease, compared with controls. In addition, an increased nuclear retention time of Smad4 was observed in fibroblasts from patients with Peyronie's disease.


CONCLUSIONS
The expression and activity of Smad transcription factors of the TGF-beta pathway is increased in fibroblasts of patients with Peyronie's disease. Alterations in the TGF-beta pathway seem to be a pathogenetic factor in the development of Peyronie's disease.
Haag
Simone M
SM
Department of Urology and Pediatric Urology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany.
Hauck
Ekkehard W
EW
Szardening-Kirchner
Carolin
C
Diemer
Thorsten
T
Cha
Eun-Sook
ES
Weidner
Wolfgang
W
Eickelberg
Oliver
O
D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D010411:Penile Induration / Q000378:metabolism*; D010413:Penis / Q000166:cytology; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D051900:Smad3 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta