The Extracellular Matrix in Dupuytren Disease

O’Gorman, David B.

doi:10.1007/978-3-319-32199-8_6

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“…To achieve these models, one obviously needs basic researchers. Human tissue-engineered models have already begun replacing animal models for preclinical drug testing 17 . Urologists with special interest in PD should organize brainstorming symposia with non-urologists such as biologists and geneticists.…”

Section: Recommendations and Conclusionmentioning

confidence: 99%

Verteporfin as a Medical Treatment in Peyronie’s Disease

et al. 2018

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IntroductionIn Europe and the United States, verteporfin (Visudyne; VP) is registered and used in treating macular degeneration. Research showed that VP decreased expression of fibrotic genes in fibroblasts collected from nodules of patients suffering from Dupuytren’s disease, plausibly by de-activating transcription in the Yes Activated Protein (YAP) pathway.AimTo analyze the effect of VP on myofibroblasts cultured from Peyronie’s disease (PD) plaques.MethodsAt surgery for PD we took biopsies from the plaques of 5 patients. By immunostaining, the presence of the pathologic myofibroblasts was determined. After culturing cells, VP was dispensed in starvation medium for 24 and 48 hours and messenger(m)RNA levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP were quantified and compared with controls with real-time polymerase chain reaction.Main Outcome MeasuremRNA-levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP.ResultsThe pathologic phenotype of cells isolated from PD plaques was confirmed with baseline immunofluorescent stainings that showed considerable levels of α-smooth muscle actin, being a marker for the presence of myofibroblasts. The mRNA ratios of all the genes related to fibrosis (COL1A1, etc.) 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.ConclusionIn our opinion, urologists must move the focus to disease before deformity, and the search for new oral or intralesional agents, well-tolerated and effective in both the acute and chronic phase of PD must continue. VP blocked the expression of genes related to fibrosis in the YAP cascade in myofibroblasts derived from PD plaque.Mohede DCJ, de Jong IJ, Bank RA, et al. Verteporfin as a medical treatment in Peyronie’s disease. Sex Med 2018;6:302–308.

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Section: Recommendations and Conclusionmentioning

confidence: 99%