Elsevier

Urology

Volume 64, Issue 2, August 2004, Pages 399-404
Urology

Basic science
Comparison of gene expression profiles between Peyronie's disease and Dupuytren's contracture

https://doi.org/10.1016/j.urology.2004.04.006Get rights and content

Abstract

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 TMβ10 and TMβ4; (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.

Section snippets

Tissues and cell cultures

PD plaques were excised from the penis of 9 patients who underwent tunica incision/excision and/or venous grafting or insertion of a penile prosthesis. The control TA tissue was obtained from 2 patients undergoing penectomy to treat penile cancer (tissue distant from the tumor) and 7 patients with erectile dysfunction undergoing penile prosthesis surgery who did not have PD. The mean patient age for those with PD was 58 years (range 54 to 62) and for those with normal TA was 59 years (range 43

Results

A series of 15 genes were upregulated and none were downregulated in the PD plaque versus the normal TA in at least 2 of the 9 patients. In the DD nodules versus the control ligament, 16 and 3 genes were upregulated and downregulated, respectively, in at least 4 of the patients. In the fibroblasts cultured from the PD plaque compared with the ones from the normal TA, 10 genes were upregulated and none were downregulated.

Table I shows that eight genes relevant to fibrosis were upregulated in

Comment

These data extend and confirm our preliminary results demonstrating the usefulness of the DNA microarrays to define changes in mRNA levels in PD in relation to normal TA1, 13 and establish the first comparison of multiple gene expression in two fibrotic conditions, PD and DD, which are frequently associated. In addition, this method identified genes that undergo changes of expression in the PD fibroblast cultures similar to those found in the original PD tissue. Three main features were

Conclusions

By looking at the endogenous pattern of gene expression, this study provides targets of potential pharmacologic modulation of the levels of genes associated with antifibrotic mechanisms. An obvious strategy is the upregulation of TMSB and decorin and, alternatively, the activation of MMPs by downregulation of their inhibitors. The stimulation of myofibroblast apoptosis and blockade of its differentiation with Rho inhibitors or cortactin may be also beneficial, because accumulation of these

Acknowledgements

To Dr. Martin Gelbard for kindly providing PD specimens.

References (32)

  • P. Angel et al.

    Function of AP-1 target genes in mesenchymal-epithelial cross-talk in skin

    Biochem Pharmacol

    (2002)
  • A. Kaufmann et al.

    Defense against influenza A virus infectionessential role of the chemokine system

    Immunobiology

    (2001)
  • T.M. Mills et al.

    Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection

    Eur J Pharmacol

    (2002)
  • K.J. Barnham et al.

    Structure of the Alzheimer's disease amyloid precursor protein copper binding domaina regulator of neuronal copper homeostasis

    J Biol Chem

    (2003)
  • S.S. Gholami et al.

    Peyronie's diseasea review

    J Urol

    (2002)
  • H. Davila et al.

    Fibrin induction of a Peyronie's-like plaque in the rat penile tunica albugineaa new model for Peyronie's disease

    Br J Urol

    (2003)
  • Cited by (118)

    • Traction and vacuum devices

      2020, Peyronie's Disease: Pathophysiology and Treatment
    View all citing articles on Scopus

    These studies were funded mainly by a grant from the Eli and Edythe L. Broad Foundation and in part by National Institute of Health grants R01DK-53069 and G12RR-03026.

    View full text