Molecular mechanisms of the itch sensation and skin inflammation induced by epidermal tight junction barrier deficiency
| Project/Area Number |
15K15422
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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(信濃町), 准教授 (70335256)
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| Co-Investigator(Renkei-kenkyūsha) |
KUBO Akiharu 理化学研究所, 統合生命医科学研究センター, チームリーダー (50452272)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥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 / かゆみ / アトピー性皮膚炎 / クローディン１ / 角質バリア / 角質 / クローディン1 / ランゲルハンス細胞 / 皮膚炎 |
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| Outline of Final Research Achievements |
The stratum corneum (SC) and tight junctions (TJs) form physical barriers in the skin. A congenital TJ barrier defect caused by a deficiency of claudin-1, which encodes a major epidermal TJ adhesion molecule, results in early neonatal death in mice and neonatal ichthyosis-sclerosing cholangitis syndrome in humans. These observations suggest the essential role of TJs in skin homeostasis. Here, we established tamoxifen (TAM)-inducible epidermis-specific claudin-1 knockout mice (K14-creERT+/-, Cldn1flox/flox mice) and investigated the pathophysiology of epidermal TJ defects in adult mice. To clarify the barrier defects of the SC and TJ separately, we measured water evaporation through isolated SC sheets (WETIS) ex vivo.On day 8, claudin-1 staining disappeared, but no elevation of WETIS was observed. On day 18, compact hyperkeratosis and increased WETIS were observed, suggesting that the TJ barrier leakage secondarily induced the SC barrier defect.
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Report
(3 results)
Research Products
(10 results)
