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Wounds in patients with neurofibromatosis type 1 (NF1) become inconspicuous and lack the tendency to form abnormal scars. We hypothesized that there would be a unique response to mechanical stimulation and subsequent scar formation in NF1. To test this hypothesis, we investigated the molecular mechanisms of differentiation into myofibroblasts in NF1\u2010derived fibroblasts and neurofibromin\u2010depleted fibroblasts and examined actin dynamics, which is involved in fibroblast differentiation, with a focus on the pathway linking LIMK2\/cofilin to actin dynamics. In normal fibroblasts, expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), a marker of myofibroblasts, significantly increased after mechanical stimulation, whereas in NF1\u2010derived and neurofibromin\u2010depleted fibroblasts, \u03b1\u2010SMA expression did not change. Phosphorylation of cofilin and subsequent actin polymerization did not increase in NF1\u2010derived and neurofibromin\u2010depleted fibroblasts after mechanical stimulation. Finally, in normal fibroblasts treated with Jasplakinolide, an actin stabilizer, \u03b1\u2010SMA expression did not change after mechanical stimulation. Therefore, when neurofibromin was dysfunctional or depleted, subsequent actin polymerization did not occur in response to mechanical stimulation, which may have led to the unchanged expression of \u03b1\u2010SMA. We believe this molecular pathway can be a potential therapeutic target for the treatment of abnormal scars.<\/jats:p>","DOI":"10.1111\/exd.14933","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T08:35:12Z","timestamp":1695112512000},"page":"2012-2022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Altered actin dynamics is possibly implicated in the inhibition of mechanical stimulation\u2010induced dermal fibroblast differentiation into myofibroblasts"],"prefix":"10.1111","volume":"32","author":[{"given":"Kazuya","family":"Kuroda","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Kiya","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Osaka 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