Molecular basis of transglutaminases action for hardness of epithelial tissues

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38030:Applied biochemistry-related
• Research Institution: Nagoya University
• Principal Investigator: Hitomi Kiyotaka 名古屋大学, 創薬科学研究科, 教授 (00202276)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: タンパク質架橋化酵素 / トランスグルタミナーゼ / 上皮組織 / バリア機能 / 線維症

Outline of Final Research Achievements

On the mammalian epithelial tissue stabilization for its barrier functions with toughness, transglutaminase (TGase), is possible to contribute by catalyzing specific protein cross-linking. So far, I investigated TGases in skin epidermis that are involved in barrier function by cross-linking several structural proteins using specific substrate peptides.
Based on the techniques and knowledge, I extended the molecular and biochemical analyses in the epithelial tissues such as liver, kidney, and lung, mainly focusing on the related disease, fibrosis. Substrate candidates for TGase were successfully identified and analyzed on their properties and the resulting products were analyzed its involvement in cellular function. Furthermore, for the cultured epithelium-derived cultured cells and also model organisms, mice and medaka fish, TGase gene expression was disrupted and successfully maintained and analyzed.

Free Research Field

応用生物化学

Academic Significance and Societal Importance of the Research Achievements

細胞内外のタンパク質を安定化させるタンパク質架橋化酵素が、外界と接する上皮組織において、その硬度化・安定化する際にどのように寄与しているかを明らかにしうる研究課題である。皮膚表皮に加え正常時の腎・肺などで架橋される基質群を明らかにしたこと、また過剰な硬度化に因る線維症についても、架橋化反応や産物の関与を、関連する組織や細胞レベルで初めて明らかにできた。また、これらの研究モデルとなる動物(マウス・メダカ)を確立し、解析展開の基盤を構築できた。得られた知見は組織のバリア機能として必要な硬度化のしくみ、また線維症の対応や薬剤シーズの発掘に貢献しうる。