Glimpses into the molecular pathogenesis of Peyronie’s disease

Abstract

Peyronie's disease (PD) is a fibroproliferative disease of the penis. Since little is known about the molecular pathogenesis of PD, we compared the biochemical make-up of PD plaques with normal tunica albuginea to clarify pathological processes in the scarred tissue. Protein and mRNA levels were measured in plaques and in unaffected pieces of the tunica albuginea. We investigated the presence of myofibroblasts, the deposition of collagens, and some key elements of Wnt and YAP1 signaling at protein level. The expression of 45 genes, all related to collagen homeostasis and extracellular matrix proteins, was quantified. In plaques, more myofibroblasts were present, and we observed an activation of Wnt signaling and YAP1 signaling. Increased levels of the collagens types I and III confirm the fibrotic nature of plaques. The mRNA ratio of collagen types III, IV, and VI to type I was increased. The expression of lysyl hydroxylase 3 was higher, whereas a decreased expression level was seen for fibronectin and cathepsin K. The biochemical composition of plaques was different from unaffected tunica albuginea: the relative and absolute abundance of various extracellular matrix proteins were changed, as well as the quality of collagen and the level of the collagen-degrading enzyme cathepsin K.

Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease

“…Previous studies have shown that β-catenin is significantly upregulated in cells derived from PD plaque as compared to normal TA tissue [ 136 ]. Ten Dam et al performed immunostaining of PD plaque and normal TA tissues, and found significant upregulation of several WNT ligands in the PD samples, including WNT2, 4, 5a, and 7b, as well as β-catenin [ 137 ]. These results suggest that the activation of the WNT/β-catenin signaling pathway is associated with PD development.…”

“…Activation of hedgehog signaling is caused, at least in part, by TGF-β1 signaling, which induces transcription of the profibrotic Hedgehog transcription factor GLI family zinc finger 2 (GLI2) [ 144 ]. In addition, activation of Hedgehog signaling may upregulate Wnt-2b and Wnt-5a, shown to be overexpressed in PD, and may also activate WNT/β-catenin signaling [ 137 , 145 ].…”

Intralesional low‐dose methylprednisolone for the treatment of active phase Peyronie’s disease: A single‐centre, preliminary prospective non‐randomised study

“…These studies generally focus on genetic, traumatic, and inflammatory processes. [17][18][19] However, regardless of the underlying cause, the inflammatory process that occurs later in the disease forms the basis of plaque formation. In the course of inflammation, Peyronie's disease occurs because of the production of inducible nitric oxide synthase (iNOS), which leads to an increase of nitric oxide and a corresponding increase in the production of peroxynitrite anion.…”

“…The average IIEF-5 score before treatment was 18.1 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). This score increased to 20.2 (10-25) after treatment.…”

Calcified Peyronie’s Disease Frequency on Computed Tomography

“…Peyronie’s disease (PD) is a benign condition characterized by the formation of fibrous plaque in the tunica albuginea layer of the penis. 1 , 2 It is an important condition that can cause painful penile erection, curvature deformity in the penis, shortened penile length, erectile dysfunction, and associated psychological problems. 3 , 4 The prevalence of PD varies between 0.4% and 23% in different case series.…”