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But the effect of KRT5, expressed only in keratinocytes, on melanocytes is unclear. Other pathogenic genes of DDD include <jats:italic>POFUT1<\/jats:italic>, <jats:italic>POGLUT1<\/jats:italic> and <jats:italic>PSENEN<\/jats:italic> genes, which is involved in posttranslational modification of Notch receptor. In this study, we aim to determine the ablation of keratinocyte KRT5 affect melanogenesis in melanocyte through Notch signalling pathway. Here we found that KRT5 downregulation decreased the expression of the Notch ligand in keratinocytes and Notch1 intracellular domain in melanocytes, by establishing two cell models of ablation of KRT5 in keratinocytes based on CRISPR\/Cas9 site\u2010directed mutation and lentivirus\u2010mediated shRNA. Treatment of melanocytes with Notch inhibitors had same effects with ablation of KRT5 on increase of TYR and decrease of Fascin1. Activation of Notch signalling reverses the effect of ablation of KRT5 on melanogenesis. Immunohistochemistry of DDD lesions with KRT5 gene mutation confirmed changes in the expression of relevant molecules in Notch signalling. Our research elucidates molecular mechanism of KRT5\u2010Notch signalling pathway in the regulation of melanocytes by keratinocytes, and preliminary reveal the mechanism of DDD pigment abnormality caused by <jats:italic>KRT5<\/jats:italic> mutation. These findings identify potential therapeutic targets of the Notch signalling pathway for the treatment of skin pigment disorders.<\/jats:p>","DOI":"10.1111\/exd.14761","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T18:00:23Z","timestamp":1677002423000},"page":"752-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>KRT5<\/scp> mutation regulate melanin metabolism through notch signalling pathway between keratinocytes and melanocytes"],"prefix":"10.1111","volume":"32","author":[{"given":"Weixue","family":"Jia","sequence":"first","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences &amp; 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