Basic scienceComparison of gene expression profiles between Peyronie's disease and Dupuytren's contracture☆
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.
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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.