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To investigate the role of FoxO1 in <jats:styled-content style=\"fixed-case\">HPK<\/jats:styled-content>s and effect of insulin\u2010like growth factor 1 (<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>\u20101) and isotretinoin on FoxO1 expression, <jats:styled-content style=\"fixed-case\">HPK<\/jats:styled-content>s were treated with 1.2\u00a0mmol\/L calcium chloride, 1\u201020\u00a0ng\/mL <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>\u20101 and 0.1\u201010\u00a0\u03bcmol\/L isotretinoin. Recombinant adenovirus expressing FoxO1 or <jats:styled-content style=\"fixed-case\">FKHR<\/jats:styled-content> sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> lentivirus transfection was introduced to upregulate or silence FoxO1 expression. Epidermal FoxO1 immunostaining was lower in acne lesion than in normal skin. FoxO1 overexpression induced involucrin expression, G2\/M arrest and apoptosis but suppressed proliferation, while FoxO1 silencing decreased involucrin expression but increased proliferation, S phase and viable cells in <jats:styled-content style=\"fixed-case\">HPK<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>\u20101 downregulated FoxO1 and involucrin but upregulated p\u2010Akt expression in <jats:styled-content style=\"fixed-case\">HPK<\/jats:styled-content>s, which was blocked by pretreatment with <jats:styled-content style=\"fixed-case\">LY<\/jats:styled-content>294002. Isotretinoin enhanced FoxO1, p53 and p21 but inhibited p\u2010FoxO1 and involucrin expression in <jats:styled-content style=\"fixed-case\">HPK<\/jats:styled-content>s. These results demonstrate that FoxO1 promotes differentiation and apoptosis in <jats:styled-content style=\"fixed-case\">HPK<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>\u20101 may reduce keratinocyte differentiation through <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/FoxO1 pathway, while isotretinoin can reinforce FoxO1 expression. FoxO1 may be involved in acne pathogenesis and could serve as a potential therapeutic target.<\/jats:p>","DOI":"10.1111\/exd.13775","type":"journal-article","created":{"date-parts":[[2018,8,25]],"date-time":"2018-08-25T10:25:27Z","timestamp":1535192727000},"page":"1254-1260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["FoxO1 enhances differentiation and apoptosis in human primary keratinocytes"],"prefix":"10.1111","volume":"27","author":[{"given":"Ge","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Yu","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Lin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Xue","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man\u2010Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi\u2010Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan\u2010Hua","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6206-1306","authenticated-orcid":false,"given":"Yi\u2010Ming","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0002"},{"key":"e_1_2_9_3_1","first-page":"1861","volume":"2017","author":"Tsitsipatis D.","journal-title":"Biochim. 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