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So far, treatments do not directly interfere with the (myo)fibroblasts that are responsible for the formation of the collagen-rich cords and its contraction. Here we investigated whether verteporfin (VP) is able to inhibit the activation and subsequent differentiation of DD nodular fibroblasts into myofibroblasts. Fibroblasts were isolated from nodules of 7 Dupuytren patients. Cells are treated (1) for 48\u00a0h with 5\u00a0ng\/ml transforming growth factor \u03b21 (TGF-\u03b21) followed by 48\u00a0h with\/without 250\u00a0nM VP in the absence of TGF-\u03b21, or treated (2) for 48\u00a0h with TGF-\u03b21 followed by 48\u00a0h with\/without VP in the presence of TGF-\u03b21. mRNA levels were measured by means of Real-Time PCR, and proteins were visualized by means of Western blotting and\/or immunofluorescence. Quantitative data were statistically analyzed with GraphPad Prism using the paired t-test. We found that fibroblasts activated for 48\u00a0h with TGF-\u03b21 show a decrease in mRNA levels of <jats:italic>COL1A1<\/jats:italic>, <jats:italic>COL3A1<\/jats:italic>, <jats:italic>COL4A1<\/jats:italic>, <jats:italic>PLOD2<\/jats:italic>, <jats:italic>FN1EDA<\/jats:italic>, <jats:italic>CCN2<\/jats:italic> and <jats:italic>SERPINE1<\/jats:italic> when exposed for another 48\u00a0h with VP, whereas no decrease is seen for <jats:italic>ACTA2<\/jats:italic>, <jats:italic>YAP1, SMAD2<\/jats:italic> and <jats:italic>SMAD3<\/jats:italic> mRNA levels. Cells exposed for an additional 48\u00a0h with TGF-\u03b21, but now in the presence of VP, are not further activated anymore, whereas in the absence of VP the cells continue to differentiate into myofibroblasts. Collagen type I, fibronectin-extra domain A, \u03b1-smooth muscle actin, YAP1, Smad2 and Smad3 protein levels were attenuated by both VP treatments. We conclude that VP has strong anti-fibrotic properties: it is able to halt the differentiation of fibroblasts into myofibroblasts, and is also able to reverse the activation status of fibroblasts. The decreased protein levels of YAP1, Smad2 and Smad3 in the presence of VP explain in part the strong anti-fibrotic properties of VP. Verteporfin is clinically used as a photosensitizer for photodynamic therapy to eliminate abnormal blood vessels in the eye to attenuate macular degeneration. The antifibrotic properties of VP do not rely on photo-activation, as we used the molecule in its non-photoinduced state.<\/jats:p>","DOI":"10.1038\/s41598-022-18116-9","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T11:04:46Z","timestamp":1660734286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Verteporfin ameliorates fibrotic aspects of Dupuytren\u2019s disease nodular fibroblasts irrespective the activation state of the cells"],"prefix":"10.1038","volume":"12","author":[{"given":"Nataly","family":"Puerta Cavanzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie A.","family":"Riesmeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris L.","family":"Holt-Kedde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M. 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