ESSM Newsletter # 40

25 ESSM Today Have you read? Best of the best: Basic research tion, and myofibroblast differentiation with an increased myofibroblast activity, resulting in increased extra-cellular matrix (ECM) protein production and eventual plaque formation, suggesting a pivotal role for myofibroblasts in the pathophysiology of PD. Several studies have shown that adenosine receptors play different roles in acute and chronic injuries and have been suggested to promote fibrosis in several organs. Adenosine and adenosine receptors have been studied in other fibrotic diseases but scarcely in PD. In order to inves- tigate the role of adenosine receptors in my- ofibroblast transformation in PD, the authors isolated fibroblasts from the non-PD TA tissue and PD plaque tissue and were transformed into myofibroblasts using transforming growth factor (TGF)- β 1. Quantification of α -smooth muscle actin and adenosine receptors (adeno- sine receptor A1 [ADORA1], adenosine recep- tor A2A, adenosine receptor A2B [ADORA2B], and adenosine receptor A3) was performed using immune cytochemistry, in-cell enzyme- linked immuno-sorbent assay (ICE), and real- time reverse transcription quantitative poly- merase chain reaction. The effect of various adenosine receptor agonists or antagonists on TGF -β 1-induced myofibroblast transformation was measured using ICE. The experiments showed that the protein and messenger RNA levels of α -smooth muscle actin in non-PD TA cells and PD plaque-derived cells were significantly higher in cells exposed to TGF- β 1 than those not treated with TGF- β 1 and that 2 of 4 adenosine receptors (ADORA1 and ADORA2B) were found to be expressed in both cell populations. Among various adenosine receptor agonists/antagonist investigated, only ADORA2B agonist, BAY 60-6583, significantly inhibited myofibroblast transformation in a concentration-dependent manner when ap- plied simultaneously with TGF- β 1. The authors concluded that ADORA2B agonists may be a novel potential therapeutic target for PD if applied during early, non-stable phase of PD. Mohede DCJ, de Jong IJ, Bank RA, van Driel MF. Verteporfin as a medical treatment in Peyronie’s disease. Sex Med. 2018; 6(4): 302-308 Verteporfin is registered in the United States and Europe as a sensitizer for photodynamic therapy to eradicate abnormal blood vessels in the eye associated with the wet form of macular degeneration. VP accumulates in the abnormal blood vessels. When stimulated by non-thermal red light (wavelength 693 nm) in the presence of oxygen, VP produces reactive short-lived singlet oxygen and other oxygen radicals, locally damaging the endothelium and resulting in blockage of these vessels. Research showed that VP decreased expres- sion of fibrotic genes in fibroblasts collected from nodules of patients suffering from Du- puytren’s disease, plausibly by de-activating transcription in the Yes Activated Protein (YAP) pathway. It has also been shown that inactive VP attenuates renal fibrosis in mice subjected to unilateral ureteral obstruction, probably by blocking the transcriptional acti- vation of targets in the YAP cascade involved in fibrosis-related processes. The objective of the present study was to determine whether VP would have similar effects on (myo)fibro- blasts derived from plaques in patients with Peyronie’s Disease (PD). The authors took bi- opsies, at the time of surgery for PD, from the plaque in 5 patients. To confirm the pathologic phenotype of cells isolated from PD plaques, baseline immunofluorescent stainings were performed that showed considerable levels of α -SMA, being a marker for the presence of myofibroblasts. The mRNA ratios of all the genes related to fibrosis except YAP decreased significantly after treatment with VP within 24 and 48 hours. These results suggest inhibition of fibrosis in the YAP cascade, downstream of YAP and that VP might benefit patients mostly in the acute phase of PD, but possibly also in the chronic phase. MJCSM The Multidisciplinary Joint Committee of Sexual Medicine Certified Sexual Medicine Training Centers 1. Porterbrook Clinic Sheffield, UK 2. Neurourology Unit, Department of Urology, Rambam Medical Center Haifa, Israel 3. Hamburg Training Centre for Sexual Medicine Hamburg, Germany 4. University Hospital Basel Basel, Switzerland 5. Clinic of Urology and Pediatric Urology, University Hospital Erlangen, Germany Become a Fellow of the European Committee of Sexual Medicine (FECSM) Become a Certified Trained Center www.mjcsm.org With support of