Peyronie's disease (PD) is a benign, progressive fibrotic disorder characterized by scar or plaques within the tunica albuginea (TA) of the penis. This study provides new insights into the pathogenesis of PD based on data from different studies regarding the roles of cytokines, cell signaling pathways, biochemical mechanisms, genetic factors responsible for fibrogenesis. A growing body of literature has shown that PD is a chronically impaired, localized, wound healing process within the TA and the Smith space. It is caused by the influence of different pathological stimuli, most often the effects of mechanical stress during sexual intercourse in genetically sensitive individuals with unusual anatomical TA features, imbalanced matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP), and suppressed antioxidant systems during chronic inflammation. Other intracellular signal cascades are activated during fibrosis along with low expression levels of their negative regulators and transforming growth factor-β1 signaling. The development of multikinase agents with minimal side effects that can block several signal cell pathways would significantly improve fibrosis in PD tissues by acting on common downstream mediators.
Chronic diseases and translational medicine. 2020 Jul 27*** epublish ***
Denis V Krakhotkin, Volodymyr A Chernylovskyi, Alexandre Mottrie, Francesco Greco, Ruslan A Bugaev
Outpatient Department, Central District Hospital, Kamenolomni, Rostov Region, Russia., Department of Urology 1, City Clinical Hospital № 4, Dnipro, Ukraine., Department of Urology, Onze Lieve Vrouw Hospital, Aalst, Belgium., Department of Urology, Humanitas Gavazzeni, Bergamo, Italy.