Krakhotkin Denis V, Chernylovskyi Volodymyr A, Mottrie Alexandre, Greco Francesco, Bugaev Ruslan A
Outpatient Department, Central District Hospital, Kamenolomni, Rostov Region, Russia.
Department of Urology 1, City Clinical Hospital № 4, Dnipro, Ukraine.
Chronic Dis Transl Med. 2020 Jul 27;6(3):165-181. doi: 10.1016/j.cdtm.2020.06.001. eCollection 2020 Sep.
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.
佩罗尼氏病(PD)是一种良性、进行性纤维化疾病,其特征是阴茎白膜(TA)内出现瘢痕或斑块。本研究基于不同研究中关于细胞因子、细胞信号通路、生化机制以及负责纤维化形成的遗传因素作用的数据,为PD的发病机制提供了新的见解。越来越多的文献表明,PD是TA和史密斯间隙内长期受损的局部伤口愈合过程。它是由不同病理刺激的影响引起的,最常见的是在具有异常解剖TA特征的遗传敏感个体进行性交期间机械应力的作用、基质金属蛋白酶/金属蛋白酶组织抑制剂(MMP/TIMP)失衡以及慢性炎症期间抗氧化系统受到抑制。在纤维化过程中,其他细胞内信号级联被激活,同时其负调节因子和转化生长因子-β1信号的表达水平较低。开发具有最小副作用且能阻断多种信号细胞通路的多激酶药物,通过作用于共同的下游介质,将显著改善PD组织中的纤维化。