Comprehensive functional analysis of S100 fused-type protein family in skin barrier formation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08265
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of Toyama
• Principal Investigator: Teruhiko Makino 富山大学, 学術研究部医学系, 准教授 (90359711)
• Co-Investigator(Kenkyū-buntansha): 清水 忠道 富山大学, 学術研究部医学系, 教授 (70260396)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: S100 fused-type protein / フィラグリン / アトピー性皮膚炎

Outline of Final Research Achievements

In the present study, we comprehensively examined an association of S100 fused-type protein family, including filaggrin (FLG), filaggrin-2 (FLG2), hornerin (HRNR), trichohyalin (TCHH), trichohyalin like 1 (TCHHL1), repetin (RPTN) and cornulin (CRNN), in the barrier formation in the atopic skin. To induce atopic dermatitis (AD) skin model, 3D skin equivalents were stimulated with recombinant IL-4 and IL-13. In this skin model, expression of FLG and FLG2 were significantly decreased and expression of RPTN and TCHH were significantly increased. On the other hand, expression of FLG, CRNN, TCHHL1 were significantly decreased and expression of FLG2, HRNR and TCHH were significantly increased. These results suggest that a regulation of the expression and a function in the barrier formation in the atopic skin may be different among S100 fused-type protein family members.

Free Research Field

keratinocyte biology

Academic Significance and Societal Importance of the Research Achievements

本研究の特色はFLGとそれに類似するS100 fused-type蛋白質群の全ての分子の機能解析を同時に行ったことにある。これにより各分子の皮膚の組織構築への関与を比較検討することが可能となり、ヒト表皮角化細胞を用いた3次元皮膚モデルの解析により、ヒト皮膚における各分子の機能と疾患との関連を直接解明できる。本研究で皮膚のバリア形成において重要な役割を担い、さらにアトピー性皮膚炎と関連しうる分子が同定されつつある。さらに研究が進展すればアトピー性皮膚炎の病態解明のみならず新規治療法の開発にもつながる可能性があり、臨床医学において大きな意味を持つといえる。