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Aberrant keratinocyte differentiation and their abnormal cytokine secretion are said to contribute to <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> by activating fibroblasts. However, the signalling pathway causing the aberrant keratinocytes in <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> has remained unidentified thus far. Given that Notch signalling is crucial in initiating keratinocyte differentiation, we hypothesized that Notch signalling contributes to <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> by modulating the phenotype of keratinocytes. We found that Notch1, Notch intracellular domain, Jagged1 and Hes\u20101 were overexpressed in the epidermis of patients with <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>. Supernatants from recombinant\u2010Jagged1\u2013treated keratinocyte cultures could accelerate dermal fibroblast proliferation and collagen production. Furthermore, Jagged1 induced keratinocyte differentiation and upregulated the expression of fibrotic factors, including transforming growth factors <jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> and <jats:italic>\u03b2<\/jats:italic><jats:sub>2<\/jats:sub>, insulin\u2010like growth factor\u20101, connective tissue growth factor, vascular endothelial growth factor and epidermal growth factor, while <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content> (a Notch inhibitor) significantly suppressed these processes. In a rabbit ear model of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>, local application of <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content> downregulated the production of fibrotic factors in keratinocytes, together with ameliorated scar hyperplasia. Our findings suggest that Notch signalling contributes to <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> by modulating keratinocyte phenotype. These results provide new insights into the pathogenesis of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> and indicate a potential therapeutic target.<\/jats:p>","DOI":"10.1111\/exd.12897","type":"journal-article","created":{"date-parts":[[2015,11,14]],"date-time":"2015-11-14T08:18:37Z","timestamp":1447489117000},"page":"137-142","source":"Crossref","is-referenced-by-count":24,"title":["Aberrant Notch signalling contributes to hypertrophic scar formation by modulating the phenotype of keratinocytes"],"prefix":"10.1111","volume":"25","author":[{"given":"Bing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xijing Hospital Fourth Military Medical University Xi'an 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