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.
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Article info
Publication history
Accepted:
April 7,
2004
Received:
December 29,
2003
Footnotes
☆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.
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.