Transcriptome-wide analysis of Peyronie’s disease plaques using RNA sequencing uncovers targetable signalling pathways for medical therapy

Milenković, Uroš; Janky, Rekin’s; Hatzichristodoulou, Georgios; Renterghem, K. Van; Cellek, Selim; Bivalacqua, T.J.; Ridder, Dirk De; Albersen, Maarten

doi:10.1016/s1569-9056(19)30893-0

Cited by 3 publications

(2 citation statements)

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“…NF-kB yolunun aktivasyonu esas olarak tümör nekroz faktör-α (TNFα) ve toll-like reseptör (TLR) sinyali ile gerçekleşirken, STAT aktivasyonuna sitokinler ve tip I/II interferonlar aracılık etmektedir. [81] Apoptotik anormalliklerin de PH gelişiminde etkili olabileceği gösterilmiştir. Apoptotik genlerin ekspresyonlarının (Fas, Fas Ligand, Bcl-2, p53, caspase 3 and 8) araştırıldığı bir çalışmada, apoptotik genlerin daha düşük ekspresyonunun kollajen üreten myofibroblastların kalıcılığına neden olabileceği gösterilmiştir.…”

Section: Gen Ekspresyonuunclassified

Peyronie hastalığı patofizyolojisi

Ateş¹,

Gökçe²

2019

Androl Bul

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Peyronie hastalığı'nın (PH) uzun tarihi boyunca birçok faktör bu hastalığın potansiyel nedeni olarak öne sürülmüştür. Yedinci yüzyılda yaşamış bir Bizans imparatoru olan Heraklius'un epispadik bir meaya ve dorsal kurvatürü olan bir penise sahip olduğu ve yüzüne doğru işeyip, boşaldığı bilinmektedir. Onun bu durumu dönemin insanları tarafından öz yeğeni ile yapmış olduğu ensest evlilik ile ilişkilendirilmiş ve tanrının bir gazabı olarak görülmüştür. [1,2] Theodoric isimli bir araştırmacı 1267 yılında penis ABSTRACT Peyronie's disease (PD) is a progressive localized fibrotic disease of tunica albuginea (TA) in the penis. It is also considered as a wound healing disorder with fibrous and non-elastic scar formation and calcified plaque formation. Clinically, these plaques can cause deformities such as curvature, shortening and contraction of the penis and pain. Although the complete spectrum of etiologic factors for PD is unknown, multiple mechanisms have been proposed including trauma, impaired fibrin clearance, autoimmune and genetic factors. It is thought that delamination of bilaminar TA in the penis with repetitive microtrauma and subsequent inflammatory process may cause the development of the Peyronie plaques. The post-traumatic inflammatory process causes myofibroblast persistence and subsequent abnormal collagen accumulation. Accompanying abnormal fibrin accumulation and irregular form of elastic fibers, characteristic tunical fibrous plaque and scar formation occur and the inflammatory process is completed. Pathogenesis of PD has been tried to be demonstrated in animal models, cell cultures and clinical studies. A better understanding of the etiopathology of this disease is important for the development of treatment strategies.

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Section: Gen Ekspresyonuunclassified

Peyronie hastalığı patofizyolojisi

Ateş¹,

Gökçe²

2019

Androl Bul

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“…However, judging from our current inability to treat PD through oral or injection therapy, there must be a 'missing link' in this pathophysiological model. Recent research using state-of-the-art RNA sequencing has painted quite a different picture compared to what is currently known in PD (unpublished data) [8]. Even though there is still a high turn-over of the extracellular matrix, it seems that this process is not necessarily maintained by myofibroblasts.…”

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What role do pharmaceuticals play in the treatment of Peyronie’s disease and is there a need for new emerging drugs?

Milenković

Ilg

Cellek

et al. 2019

Expert Opinion on Emerging Drugs

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Introduction: Finding novel medical treatment for Peyronie's disease (PD) has suffered from similar limitations and difficulties as other fibrotic diseases. Areas covered: Underlying fibrosis, there is a vastly complex intertwining of several pathways. Focusing on a single target during antifibrotic drug development has not led to the development of many efficacious drugs, especially in PD. Inhibiting one cog in this large machinery usually leads to activation of compensatory mechanisms. Expert opinion: Novel strategies in drug discovery such as phenotypical drug screening and gene expression profiling technologies could provide a solution for this impasse.

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