Gene expression profiles in the Peyronie's disease plaque.
OBJECTIVE
To provide molecular insight into the pathophysiology of Peyronie's disease (PD), a preliminary profile of differential gene expression between the PD plaque and control tunica albuginea was obtained with DNA microarrays.


METHODS
Seven PD plaques and five control tunica albugineas were studied. cDNA specimens were prepared from RNA isolated from one calcified PD plaque and one control tissue and hybridized with the Clontech Atlas 1.2 Array. Another set of plaque and control RNA samples was hybridized with the Affymetrix GeneChip. Relative changes of greater than 2.0 defined up-regulation and down-regulation, respectively. RNA from the remaining tissues was used to determine, by reverse transcriptase-polymerase chain reaction and Western blot analysis, the expression of selected individual genes.


RESULTS
Some of up-regulated genes in the PD plaque detected by the Clontech assay were pleiotrophin, monocyte chemotactic protein 1, and early growth response protein, which are involved in osteoblast recruitment, inflammation, and fibroblast proliferation, respectively. Ubiquitin and Id-2, which are involved in tissue remodeling, were down-regulated. The Affymetrix DNA chips identified the up-regulation of elastase (involved in elastic fiber degradation) and the myofibroblast markers alpha and gamma-smooth muscle actin, desmin, and others, as well as the down-regulation of collagenase IV and transforming growth factor-beta modulators. Four of the five genes selected for reverse transcriptase-polymerase chain reaction and Western blotting confirmed the DNA microarray results.


CONCLUSIONS
In the PD tissue, the genes involved in collagen synthesis, myofibroblast differentiation, tissue remodeling, inflammation, ossification, and proteolysis are up-regulated, and the genes that inhibit some of these processes and collagenase are down-regulated.
Magee
Thomas R
TR
Department of Urology, University of California, Los Angeles, School of Medicine, Los Angeles, California 90509, USA.
Qian
Ansha
A
Rajfer
Jacob
J
Sander
Fred C
FC
Levine
Laurence A
LA
Gonzalez-Cadavid
Nestor F
NF
D002352:Carrier Proteins / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D051766:Early Growth Response Protein 1; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins; D051797:Inhibitor of Differentiation Protein 2; D008297:Male; D010196:Pancreatic Elastase / Q000235:genetics; D010411:Penile Induration / Q000235:genetics*; D012097:Repressor Proteins; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics; D015854:Up-Regulation
D002352:Carrier Proteins; D018932:Chemokine CCL2; D016207:Cytokines; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C497450:ID2 protein, human; D017874:Immediate-Early Proteins; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C066845:pleiotrophin; D010196:Pancreatic Elastase