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We previously identified that botulinum toxin (BTX) injection suppresses pressure ulcer formation in a cutaneous ischemia\u2013reperfusion injury mouse model by regulation of oxidative stress. However, the therapeutic possibility of BTX administration for preventing skin fibrosis in SSc is unclear. The objective of this study was to investigate the effect of BTX\u2010B on skin fibrosis in a murine model of SSc and determine the underlying mechanism. We found that BTX\u2010B injection significantly reduced dermal thickness and inflammatory cell infiltration in bleomycin\u2010induced skin fibrosis lesion in mice. We also identified that the oxidative stress signal detected through bioluminescence in OKD48 mice after bleomycin injection in the skin was significantly decreased by BTX\u2010B. Additionally, mRNA levels of oxidative stress associated factors (NOX2, HO\u20101, Trx2) were significantly decreased by BTX\u2010B. Apoptotic cells in the lesional skin of bleomycin\u2010treated mice were significantly reduced by BTX\u2010B. Oxidant\u2010induced intracellular accumulation of reactive oxygen species in SSc fibroblasts was also inhibited by BTX\u2010B. In conclusion, BTX\u2010B might improve bleomycin\u2010induced skin fibrosis via the suppression of oxidative stress and inflammatory cells in the skin. BTX\u2010B injection may have a therapeutic effect on skin fibrosis in SSc.<\/jats:p>","DOI":"10.1111\/1346-8138.15888","type":"journal-article","created":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T15:18:21Z","timestamp":1618154301000},"page":"1052-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress"],"prefix":"10.1111","volume":"48","author":[{"given":"Hritu","family":"Baral","sequence":"first","affiliation":[{"name":"Department of Dermatology Gunma University Graduate School of Medicine Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7016-337X","authenticated-orcid":false,"given":"Akiko","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Gunma University Graduate School of Medicine 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