Evaluation of the tight junction barrier impairment in the pathogenesis of atopic dermatitis
| Project/Area Number |
25670507
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
KUBO Akiharu 慶應義塾大学, 医学部, 講師 (70335256)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | タイトジャンクション / 皮膚バリア / アトピー性皮膚炎 / アレルギー / 角質バリア / バリア破綻 / 角層バリア / 皮膚バリア機能 |
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| Outline of Final Research Achievements |
The stratum corneum (SC) and tight junctions (TJs) form physical barriers in the skin. Impairment of SC and/or TJ barriers has been reported in atopic dermatitis skin, however, the direct consequence of TJ barrier dysfunction on dermatitis onset is unknown. In this study, we established tamoxifen (TAM)-inducible epidermis-specific claudin-1–knockout mice and investigated the pathophysiology of primary epidermal TJ defects in adult mice.
TJ leakage was initially observed focally on day 4 after TAM injection, and had developed fully on day 8. By contrast, the elevation of transepidermal water loss (TEWL) commenced later, on day 10, and reached its peak by day 18. The dermatitis phenotype, including erythema with scales, also became apparent on day 18. Water evaporation through the isolated SC sheets was normal on day 8 but significantly increased on day 18. Therefore, SC barrier impairment and TEWL elevation were secondarily induced after TJ leakage in this mouse model.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis2014
Author(s)
Yoshida K, Kubo A, Fujita H, Yokouchi M, Ishii K, Kawasaki H, Nomura T, Shimizu H, Kouyama K, Ebihara T, Nagao K, Amagai M.
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Journal Title
The Journal of Allergy and Clinical Immunology
Volume: 134(4)
Issue: 4
Pages: 856-864
DOI
Related Report
Peer Reviewed / Open Access
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