Comparison of gene expression profiles between Peyronie's disease and Dupuytren's contracture.
OBJECTIVE
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 TMbeta10 and TMbeta4; (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.
Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA.
A
A
Qian
R A
RA
Meals
J
J
Rajfer
N F
NF
Gonzalez-Cadavid
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000378:metabolism; D051356:Cortactin; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004387:Dupuytren Contracture / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004790:Enzyme Induction; D005205:Fascia / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010411:Penile Induration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010413:Penis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000096:biosynthesis / Q000235:genetics
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D051356:Cortactin; D016207:Cytokines; D018076:DNA, Complementary; D008840:Microfilament Proteins; C512835:POSTN protein, human; D012333:RNA, Messenger; C066845:pleiotrophin; D013947:Thymosin; D020782:Matrix Metalloproteinases