INVESTIGATIVE UROLOGY

Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture
Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF
Harbor-UCLA Research and Education Institute, Torrance, California, Department of Orthopedics and Urology, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA
Urology 2004; 64: 399-404

• Objectives: To compare the gene expression alterations in human Peyronie’s disease (PD) and Dupuytren’s disease (DD) to determine whether they share a common pathophysiology. Multiple mRNA expression profiles of human PD have previously shown that genes that regulate fibroblast replication, myofibroblast differentiation, collagen metabolism, tissue repair, and ossification are involved. DD, a palmar fascia fibrosis, may be associated with PD.
• Methods: Total RNA samples from PD plaques, normal tunica albuginea, Dupuytren’s nodules, and normal palmar fascia (nine samples per group) were subjected to differential gene expression profile analysis (Clontech Atlas DNA microarray) comparing PD with tunica albuginea and DD with normal palmar fascia. Changes of more than 2.0 in PD and DD compared with tunica albuginea and normal palmar fascia, respectively, were recorded. Reverse transcriptase-polymerase chain reactions were performed for some genes whose expression was altered in PD.
  Results: Some of the gene families upregulated in both PD and DD were (a) collagen degradation: matrix metalloproteinase (MMP), with MMP2 and MMP9, and thymosins (MMP activators), with TMb10 and TMb4; (b) ossification: osteoblast-specific factors (OSFs) OSF-1 and OSF-2 (DD only); and (c) myofibroblast differentiation: RhoGDP dissociation inhibitor 1. The genes upregulated in PD only were decorin (an inhibitor of transforming growth factor-beta1 and a part of fibroblast replication/collagen synthesis) and early growth response protein. Reverse transcriptase-polymerase chain reaction confirmed these changes.
• Conclusions: These data demonstrate that the pattern of alterations in the expression of certain gene families in PD and DD is similar, suggesting that they share a common pathophysiology and may be amenable to the same therapeutic regimens.
  
  
• Editorial Comment
  The authors present one more wonderful contribution to the knowledge of Peyronie’s disease.
  One of the most accepted etiologies for Peyronie’s disease is that it is caused by trauma to the erect penis, resulting in extravasation of fibrin and other blood proteins into the tunica albuginea that, together with other unknown factors, elicit an inflammatory reaction followed by the production of pro-fibrotic agents, such as transforming growth factor-beta1 and reactive oxygen species. Peyronie’s disease may be associated with Dupuytren’s disease, which occurs in the palmar fascia in 21% of the cases. Dupuytren’s disease is characterized by similar fibrotic alterations, although its relationship to trauma is less established.
  Analyzing gene expression, this study provides targets of potential pharmacologic modulation of the levels of genes associated with antifibrotic mechanisms. The authors speculate that stimulation of myofibroblast apoptosis and blockade of its differentiation with Rho inhibitors or cortactin may be beneficial, because accumulation of these cells in an abnormal healing process subsequent to trauma may relate to the fibrosis seen in Peyronie’s disease and Dupuytren’s disease.
  Previous studies by the same group (1) demonstrated that treatment with L-arginine and phosphodiesterase inhibitors, both stimulating apoptosis and remodeling by nitric oxide/cyclic guanosine monophosphate or cyclic guanosine monophosphate alone, respectively, has been shown to prevent the fibrotic plaque in the TGF-b animal model of Peyronie’s disease.

REFERENCE
1. Valente EG, Vernet D, Ferrini MG, Qian A, Rajfer J, Gonzalez-Cadavid NF: L-arginine and phosphodiesterase (PDE) inhibitors counteract fibrosis in the Peyronie’s fibrotic plaque and related fibroblast cultures. Nitric Oxide. 2003; 9: 229-44.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil