{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:47Z","timestamp":1787013947593,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate which phosphodiesterase (PDE) isoforms are expressed in fibroblasts isolated from the tunica albuginea (TA) of patients with Peyronie's disease (PD), and to measure the potency of PDE inhibitors in preventing transformation of these fibroblasts to profibrotic myofibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Fibroblasts isolated from the TA of men undergoing surgery for correction of PD curvature were transformed to myofibroblasts using transforming growth factor beta\u20101. The expression of 21 PDE isoforms was investigated using quantitative reverse transcriptase\u2010polymerase chain reaction and protein analysis, as were the effects of various PDE inhibitors on prevention of myofibroblast transformation. Intracellular cAMP and cGMP in the presence of PDE inhibitors were quantified using cGMP\/cAMP enzyme\u2010linked immunosorbant assay assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that PDE1A, 1C, 4, 5A, 7B and 8B were expressed at mRNA and protein levels. Selective inhibitors of these enzymes prevented myofibroblast transformation in a concentration\u2010dependent manner, with PDE1 inhibitor ITI\u2010214 and PDE4 inhibitors roflumilast and roflumilast N\u2010oxide showing greatest potency. ITI\u2010214 and roflumilast N\u2010oxide increased intracellular cAMP, but not cGMP, in a concentration\u2010dependent manner.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first demonstration of the expression of PDE1, 7 and 8 isoforms, and the function of PDE1 and PDE4 in human TA fibroblasts. The ability of inhibitors of these enzymes to prevent myofibroblast transformation suggests that such inhibitors can be developed to treat acute PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.16631","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:09:01Z","timestamp":1734998941000},"page":"810-817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of phosphodiesterases 1 and 4 prevents myofibroblast transformation in Peyronie's disease"],"prefix":"10.1111","volume":"135","author":[{"given":"Sophie L.","family":"Harding","sequence":"first","affiliation":[{"name":"Fibrosis Research Group, Medical Technology Research Centre Anglia Ruskin University  Chelmsford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus M.","family":"Ilg","sequence":"additional","affiliation":[{"name":"Fibrosis Research Group, Medical Technology 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