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This study aims to investigate the mechanism of calycosin related to tight junctions (<jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s) and <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 both in <jats:styled-content style=\"fixed-case\">FITC<\/jats:styled-content>\u2010induced mice allergic contact dermatitis and in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 stimulated HaCaT keratinocytes. Th2 cytokines (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013) were detected by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>. The epithelial <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content> proteins (occludin, <jats:styled-content style=\"fixed-case\">CLDN<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">ZO<\/jats:styled-content>\u20101), initiative key cytokines (<jats:styled-content style=\"fixed-case\">TSLP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201033) and <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 were assessed by Western blot, real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, immunohistochemistry or immunofluorescence. Herein, we have demonstrated that allergic inflammation and the Th2 cytokines in <jats:styled-content style=\"fixed-case\">ACD<\/jats:styled-content> mice were reduced significantly by calycosin treatment. Meanwhile, calycosin obviously decreased the expression of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 and repaired <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s both in\u00a0vivo and in\u00a0vitro. In HaCaT keratinocytes, we noted that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 induced the deterioration of <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s, as well as the increased levels of <jats:styled-content style=\"fixed-case\">TSLP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201033, which could be reversed by silencing <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1. In addition, administration of 2\u2010methoxyestradiolin (2\u2010<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>), a <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 inhibitor,significantly repaired the <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s and alleviated the allergic inflammation in\u00a0vivo. Furthermore, <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s were destroyed by <jats:styled-content style=\"fixed-case\">DMOG<\/jats:styled-content> or by overexpressing <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 in HaCaT keratinocytes, and simultaneously, calycosin down\u2010regulated the expression of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 and repaired the <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s in this process. These results revealed that calycosin may act as a potential anti\u2010allergy and barrier\u2010repair agent via regulating <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> and suggested that <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 and <jats:styled-content style=\"fixed-case\">TJ<\/jats:styled-content>s might be possible therapy targets for allergic dermatitis.<\/jats:p>","DOI":"10.1111\/jcmm.13763","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T11:13:06Z","timestamp":1531307586000},"page":"4507-4521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Calycosin alleviates allergic contact dermatitis by repairing epithelial tight junctions via down\u2010regulating HIF\u20101\u03b1"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7381-5150","authenticated-orcid":false,"given":"Zhirong","family":"Jia","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine Nanjing 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