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We used human keratinocyte models to investigate the key cornifying factors for dermatological and biological abnormalities induced by sunitinib. On the basis of the results of microarray analysis using the three\u2010dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal\u2010type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochemical staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal\u2010regulated kinases (ERK)1\/2 and phosphorylated p38 mitogen\u2010activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib\u2010induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase\u20103\u03b2 by enhancing ERK1\/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1\/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathology of HFSR.<\/jats:p>","DOI":"10.1111\/exd.14230","type":"journal-article","created":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T03:29:24Z","timestamp":1604201364000},"page":"337-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sunitinib decreases the expression of KRT6A and SERPINB1 in 3D human epidermal models"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-3562","authenticated-orcid":false,"given":"Ayaka","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Pharmacy Kobe University Hospital Kobe Japan"},{"name":"Department of Diagnostic Pathology Kobe University Graduate School of Medicine Kobe 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