New discoveries in the basic science understanding of Peyronie’s disease

Abstract

Peyronie's disease is an acquired benign condition representing localized fibrosis of the penis. The disease is caused by microvascular trauma to the penis, with subsequent fibrin deposition resulting in aberrant wound healing and possibly other etiologies. Histopathologic studies of the Peyronie's plaque have demonstrated the role of transforming growth factor-beta 1 in the pathologic development of penile plaque. Animal models have been developed to test pathophysiology and therapeutics. The role of inducible nitric oxide synthase and nitric oxide has been established to limit and counteract fibrosis. Differential gene expression studies have identified candidate up-regulated or down-regulated genes that are involved in the pathophysiology of Peyronie's disease.

Antifibrotic Synergy Between Phosphodiesterase Type 5 Inhibitors and Selective Oestrogen Receptor Modulators in Peyronie's Disease Models

“…Most important functions include production and remodelling of extracellular matrix (ECM) protein [6,9], and secretion of profibrotic and proinflammatory cytokines [9]. These cells have been shown to be present in liver [10], lung [11], and kidney [12] fibrosis as well as in PD plaques [13,14]. It is therefore generally agreed that myofibroblasts play a critical role in the pathophysiology of fibrosis.…”

Understanding the course of Peyronie's disease

“…Although the aetiology and underlying pathophysiology of PD are not completely understood, it is believed that it originates from trauma or repeated microtrauma to the erect penis in genetically susceptible men, which leads to inflammation, disruption of the elastic fibres and deposition of fibrin . The inflammatory factor, transforming growth factor (TGF)‐β1 may play an important role in induction of collagen production by fibroblasts/myofibroblasts in the development of PD plaques . Recent studies using an animal model have shown that the overexpression of TGF‐β1 induces fibroblasts to deposit collagen resulting in the formation of tunical plaques, whereas inhibitors of the TGF‐β1 receptor kinase promote the regression of fibrotic plaques and lead to a reduction in penile curvature .…”

Is There a Role for Proteomics in Peyronie's Disease?

“…This process induces a complex host response, involving recruitment of inflammatory cells and release of profibrotic factors and reactive oxygen species (ROS), that promotes a cycle of disordered wound healing between the TA and corpus cavernosum [21–23]. The end result of these processes is chronic inflammation, excessive collagen deposition and disorganization, elastin fragmentation, and eventual calcification consistent with a PD plaque [24].…”

“…TGF‐β is a multifunctional pleiotropic protein that induces extracellular matrix synthesis, inhibits collagen degradation, stimulates differentiation of fibroblasts into myofibroblasts, induces ROS formation, and inhibits nitric oxide (NO) synthesis by repressing inducible nitric oxide synthase (iNOS), thus lowering the NO‐to‐ROS ratio [24,25,27,28]. In normal tissues, fibrosis is counteracted by the expression of iNOS, which produces NO that has an antifibrotic role by inhibiting TGF‐β, neutralizing reactive oxygen species, reducing myofibroblast differentiation, and promoting collagen breakdown by activating MMPs [27–31].…”