{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:17:37Z","timestamp":1788880657280,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T00:00:00Z","timestamp":1546732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003946","name":"European Society for Sexual Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To uncover the anti\u2010myofibroblast (MFB) properties of Rho\u2010kinase inhibitor (compound Y\u201027632) and simvastatin in an\n                      <jats:italic>in\u00a0vitro<\/jats:italic>\n                      model of Peyronie's disease (PD), a sexually debilitating disease caused by an irreversible fibrotic plaque in the penile tunica albuginea (TA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Primary human fibroblasts (FBs) were isolated from surgically obtained TA tissue from patients with PD. To induce MFB status, cells were stimulated with 3\u00a0ng\/mL transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21). Increasing doses of Y\u201027632 and simvastatin were added. Real\u2010time quantitative PCR was used to assess mRNA expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), collagen III, elastin and connective tissue growth factor (CTGF) after 72\u00a0h. Western blot analysis was used to quantify \u03b1\u2010SMA protein contents, and immunofluorescence (IF) was used to visualize MFB differentiation by staining for \u03b1\u2010SMA after 72\u00a0h. A resazurin\u2010based assay was used to assess cell viability to ensure the anti\u2010MFB effect of the drugs. A mechanistic study was performed using IF staining for YAP\/TAZ nuclear translocation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 72\u00a0h of stimulation with TGF\u2010\u03b21, a six\u2010 to 10\u2010fold upregulation of \u03b1\u2010SMA could be observed. When treated with Y\u201027632 or simvastatin, the \u03b1\u2010SMA, collagen III, elastin and CTGF mRNA expression was impeded. Additionally, TGF\u2010\u03b21 stimulation showed a twofold increase in \u03b1\u2010SMA protein expression, which was reversed to non\u2010stimulated levels after treatment with Y\u201027632 and simvastatin. Using IF, stimulated cells were identified as MFB (\u03b1\u2010SMA+, Vim+) as opposed to the non\u2010stimulated, Y\u201027632\u2010 and simvastatin\u2010treated cells (\u03b1\u2010SMA\u2212, Vim+). The resazurin\u2010based assay confirmed that the cell viability was not compromised by the administered drugs. On stimulation with TGF\u2010\u03b21, nuclear translocation of YAP\/TAZ could be observed, which was prevented by adding the aforementioned compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Transformation of FBs into the contractile and extracellular matrix\u2010producing MFBs occurs after TGF\u2010\u03b21 stimulation. In our experiments, Rho\u2010kinase inhibition and simvastatin treatment were shown to prevent this in TGF\u2010\u03b21\u2010stimulated cells on an RNA and protein level through the inhibition of YAP\/TAZ nuclear translocation. Y\u201027632 and simvastatin could become a novel treatment option in the early treatment of PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.14638","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T00:36:10Z","timestamp":1544402170000},"page":"703-715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Simvastatin and the Rho\u2010kinase inhibitor Y\u201027632 prevent myofibroblast transformation in Peyronie's disease\u2010derived fibroblasts via inhibition of YAP\/TAZ nuclear translocation"],"prefix":"10.1111","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-2534","authenticated-orcid":false,"given":"Uros","family":"Milenkovic","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Urology Department of Development and Regeneration KU Leuven Leuven Belgium"},{"name":"Department of Urology University Hospitals Leuven Leuven 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