Evaluation of the tight junction barrier impairment in the pathogenesis of atopic dermatitis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670507
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: KUBO Akiharu 慶應義塾大学, 医学部, 講師 (70335256)
• Project Period (FY): 2013-04-01 – 2015-03-31
• 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

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.

Free Research Field

細胞生物学、皮膚科学