title: Gene expression in Peyronie's disease.
abstract: Currently, surgical intervention is the only efficacious treatment for Peyronie's disease (PD), a fibromatosis of the tunica albuginea of the penis. Therapies based on the molecular pathways for this disease could provide alternatives to surgical treatment but only recently has the pathophysiology of the Peyronie's disease plaque been investigated at the molecular level. In this review, we examine the current knowledge of gene expression in the PD plaque and the relationship of PD with other fibrotic conditions such as Dupytren's disease. TGFbeta1, along with other growth factors, pro-fibrotic genes, and collagen, are expressed in fibroblasts and myofibroblasts. Myofibroblasts are normally involved in wound contracture and largely eliminated via apoptosis during the late stages of wound remodeling. In the PD plaque, however, these cells persist and may play an important role in the PD plaque fibrosis. The expression levels of TGFbeta1 and pro- and anti-fibrotic gene products, along with the nitric oxide/reactive oxygen species (NO/ROS) ratio in the tunica albuginea, appear to be essential for the formation and progression of the PD plaque and effect the expression of multiple genes. This can be assessed with the recently developed DNA-based chip arrays and results with the PD plaque have been encouraging. OSF-1 (osteoblast recruitment), MCP-1 (macrophage recruitment), procollagenase IV (collagenase degradation), and other fibrotic genes have been identified as being possible candidate regulatory genes. Finally, possible therapeutic avenues for gene-based therapy in the treatment of PD are discussed that may eventually reduce the need for surgical intervention.
authors.affiliation: Department of Urology, UCLA School of Medicine, Los Angeles, California, USA. ncadavid@ucla.edu
authors.forename: N F
authors.initials: NF
authors.lastname: Gonzalez-Cadavid
authors.forename: T R
authors.initials: TR
authors.lastname: Magee
authors.forename: M
authors.initials: M
authors.lastname: Ferrini
authors.forename: A
authors.initials: A
authors.lastname: Qian
authors.forename: D
authors.initials: D
authors.lastname: Vernet
authors.forename: J
authors.initials: J
authors.lastname: Rajfer
mesh_terms: D000818:Animals; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D008297:Male; D010411:Penile Induration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*