{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T19:28:58Z","timestamp":1767986938553,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,10,14]],"date-time":"2018-10-14T00:00:00Z","timestamp":1539475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Key R&D Program of China","award":["2017YFC1103300"],"award-info":[{"award-number":["2017YFC1103300"]}]},{"name":"National Key R&D Program of China","award":["2017YFC1104700"],"award-info":[{"award-number":["2017YFC1104700"]}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81721092"],"award-info":[{"award-number":["81721092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PLA General Hospital Science and Technology Innovation Nursery Fund Project","award":["16KMM52"],"award-info":[{"award-number":["16KMM52"]}]},{"name":"Key Research and Development Project of Hainan","award":["ZDYF2016135"],"award-info":[{"award-number":["ZDYF2016135"]}]},{"name":"Key Research and Development Project of Hainan","award":["ZDYF2017095"],"award-info":[{"award-number":["ZDYF2017095"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tissue contraction and the extracellular matrix deposition are part of the pathogenesis of hypertrophic scars. The transcriptional factor NFE2L2 inhibits fibroblast differentiation in idiopathic pulmonary fibrosis and promotes myofibroblast dedifferentiation. Our previous study showed that the transcription factor NFE2L2 was strongly induced on treatment with arsenic trioxide (ATO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The present study sought to investigate the effect of ATO on myofibroblast formation to determine its potential role in hypertrophic scar treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Small interfering RNA against NFE2L2 was used on treatment with ATO in human skin myofibroblasts. The expression levels of fibrosis markers were assessed by reverse transcription polymerase chain reaction, western blot, and immunofluorescence staining. The transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21)\/Smad2\/3 signaling was detected by western blot. A rabbit ear model was used to evaluate the antifibrotic role of ATO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the cellular level, ATO abolished fibroblast differentiation in response to TGF\u2010\u03b21. ATO reduced TGF\u2010\u03b21\u2010induced reactive oxygen species accumulation through increased expression of the antioxidant gene HO\u20101 in fibroblasts. In addition, ATO promoted the nuclear translocation of NFE2L2 and inhibited the phosphorylation of Smad2\/3. In the rabbit ear model, ATO prevented the progression of hypertrophic scar formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides the first evidence implying that ATO inhibits the formation of myofibroblasts in vivo and in vitro and provides a possible treatment for hypertrophic scars.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.27073","type":"journal-article","created":{"date-parts":[[2018,10,14]],"date-time":"2018-10-14T12:04:51Z","timestamp":1539518691000},"page":"2606-2617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Arsenic trioxide inhibits the differentiation of fibroblasts to myofibroblasts through nuclear factor erythroid 2\u2010like 2 (NFE2L2) protein and the Smad2\/3 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