• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular basis of transglutaminases action for hardness of epithelial tissues

Research Project

Project/Area Number 18H02134
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38030:Applied biochemistry-related
Research InstitutionNagoya 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
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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 / タンパク質架橋 / 表皮 / 上皮 / タンパク質架橋化
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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (47 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (35 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Thrombin-deficient mutant of medaka, a model fish, displays serious retardation in blood coagulation.2021

    • Author(s)
      Watanabe Y., Oguri R., Suzuki R., Ishikawa Y., Tatsukawa H., Hashimoto H., Hitomi K.
    • Journal Title

      Biosceince, Biochemistry and Biotechnology

      Volume: 85 Issue: 4 Pages: 824-833

    • DOI

      10.1093/bbb/zbaa098

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transglutaminase orthologues in medaka fish - biochemical characterization and establishment of gene-deficient mutants2020

    • Author(s)
      Meng Qi、Watanabe Yuko、Suzuki Risa、Oguri Rina、Tatsukawa Hideki、Hitomi Kiyotaka
    • Journal Title

      Analytical Biochemistry

      Volume: - Pages: 113610-113610

    • DOI

      10.1016/j.ab.2020.113610

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of substrates crosslinked by transglutaminases in liver and kidney fibrosis2020

    • Author(s)
      Tatsukawa Hideki、Takeuchi Taishu、Shinoda Yoshiki、Hitomi Kiyotaka
    • Journal Title

      Analytical Biochemistry

      Volume: - Pages: 113629-113629

    • DOI

      10.1016/j.ab.2020.113629

    • NAID

      120006941034

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the expression of transglutaminases in the reconstructed human epidermis using a three-dimensional cell culture2020

    • Author(s)
      Teshima Hirofumi、Kato Manami、Tatsukawa Hideki、Hitomi Kiyotaka
    • Journal Title

      Analytical Biochemistry

      Volume: - Pages: 113606-113606

    • DOI

      10.1016/j.ab.2020.113606

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene disruption of medaka (Oryzias latipes) orthologue for mammalian tissue-type transglutaminase (TG2) causes movement retardation2020

    • Author(s)
      Watanabe Yuko、Okuya Kazuho、Takada Yuki、Kinoshita Masato、Yokoi Saori、Chisada Shinichi、Kamei Yasuhiro、Tatsukawa Hideki、Yamamoto Naoyuki、Abe Hideki、Hashimoto Hisashi、Hitomi Kiyotaka
    • Journal Title

      The Journal of Biochemistry

      Volume: - Issue: 3 Pages: 213-222

    • DOI

      10.1093/jb/mvaa038

    • NAID

      40022375409

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 血液凝固のメカニズムと病態について魚類を用いて解析する2019

    • Author(s)
      鈴木里沙、Qi Meng, 渡辺優子、人見清隆
    • Journal Title

      化学と生物

      Volume: 57 Pages: 359-365

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Studies on differentiation-dependent expression and activity of distinct transglutaminases by specific substrate peptides using three dimensional reconstituted epidermis.2019

    • Author(s)
      Tanabe Y., Yamane M, Kato M., Teshima H., Kuribayashi M., Tatsukawa H., Takama H., Akiyama M.,  Hitomi K.
    • Journal Title

      FEBS J.

      Volume: in press Issue: 13 Pages: 2536-2548

    • DOI

      10.1111/febs.14832

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transglutaminase family in Medaka, a model fish2018

    • Author(s)
      渡邉優子、人見清隆
    • Journal Title

      生化学

      Volume: 90 Issue: 4 Pages: 491-494

    • DOI

      10.14952/SEIKAGAKU.2018.900491

    • NAID

      40021670581

    • ISSN
      0037-1017
    • Year and Date
      2018-08-25
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Isozyme-specific comprehensive characterization of transglutaminase-crosslinked substrates in kidney fibrosis2018

    • Author(s)
      Tatsukawa Hideki、Otsu Risa、Tani Yuji、Wakita Ryosuke、Hitomi Kiyotaka
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 7306-7306

    • DOI

      10.1038/s41598-018-25674-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting transglutaminase 2 partially restores extracellular matrix structure but not alveolar architecture in experimental bronchopulmonary dysplasia.2018

    • Author(s)
      MizikoVa I, Pfeffer T, Nardiello C, Surate Solaligue DE, Steenbock H, Tatsukawa H, Silva DM, Hitomi K, Morty RE.他6名
    • Journal Title

      FEBS J.

      Volume: 285 Issue: 16 Pages: 3056-3076

    • DOI

      10.1111/febs.14596

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection and identification of potential transglutaminase 2 substrates in the mouse renal glomeruli.2018

    • Author(s)
      Ito Y., Tatsukawa H., Yamaguchi H., Takahashi K., Hitomi K., and Yuszawa Y.
    • Journal Title

      Arch. Biochem. Biophys.

      Volume: 660 Pages: 11-19

    • DOI

      10.1016/j.abb.2018.10.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spatial arrangement of proteins using scCro-tag: application for an in situ enzymatic microbead assay.2018

    • Author(s)
      Kojima T., Hata J, Hayashi K., Hitomi K,Nakano H.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 82 Issue: 11 Pages: 1911-1921

    • DOI

      10.1080/09168451.2018.1501265

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 組織線維化におけるタンパク質架橋反応の分子標的の解明研究2020

    • Author(s)
      辰川英樹、篠田祥希、竹内大修、人見清隆
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マクロファージの極性化に関わるタンパク質架橋化酵素の解析2020

    • Author(s)
      篠田祥希、辰川英樹、人見清隆
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肺線維化においてタンパク質架橋化酵素により架橋される基質のプロテオミクス解析2020

    • Author(s)
      竹内大修、桑田啓子、辰川英樹、人見清隆
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Investigation for the novel functions of fibrinogen through establishing gene-deficient medaka (Oryzias latipes)2020

    • Author(s)
      Meng Qi、渡邉優子、辰川英樹、人見清隆
    • Organizer
      第43回日本分子生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 羊水中に存在する表皮細胞分化制御成分の性状解析2020

    • Author(s)
      栗林美樹、川口友輔、手島裕文、山口央輝、辰川英樹、人見清隆
    • Organizer
      第43回日本分子生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 空気暴露が促進する表皮分化メカニズムの解析2020

    • Author(s)
      手島裕文、辰川英樹、人見清隆
    • Organizer
      第43回日本分子生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] M2型マクロファージの極性化におけるトランスグルタミナーゼの機能解析2020

    • Author(s)
      篠田祥希、辰川英樹、人見清隆
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗線維化薬ピルフェニドンの薬理作用点同定に向けた探索研究2020

    • Author(s)
      竹内大修、横島聡、辰川英樹、人見清隆
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] タンパク質架橋化酵素トランスグルタミナーゼの線維症に伴う活性変動と基質群の解析2019

    • Author(s)
      人見清隆
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎線維化において架橋修飾される新規基質タンパク質の同定と解析2019

    • Author(s)
      辰川英樹、人見清隆
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Analysis of the mechanism of transglutaminase-mediated tissue fibrosis2019

    • Author(s)
      辰川英樹、竹内大修、人見清隆
    • Organizer
      Gordon Research Conferences Tissue Repair and Regeneration
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Studies on cellular changes upon air-liquid phase stimulation in the three-dimensional keratinocyte culture system2019

    • Author(s)
      手島裕文、栗林美樹、伊藤帆南、辰川英樹、人見清隆
    • Organizer
      Gordon Research Conferences Barrier function
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection system of transglutaminase in vitro and in situ activities using specific substrate peptides in the epidermis and three-dimensional keratinocyte cultured system2019

    • Author(s)
      加藤まなみ、手島裕文、田辺勇輝、辰川英樹、人見清隆
    • Organizer
      Gordon Research Conferences Barrier function
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biochemical characterization of medaka thrombin, a blood coagulation factor, and establishment of its gene-deficient fish2019

    • Author(s)
      小栗莉奈、 鈴木里沙、Meng Qi、小栗莉奈、 渡辺優子、辰川英樹、橋本寿史、人見清隆
    • Organizer
      小型魚類研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Investigation for Medaka Orthologues of Human Fibrinogen2019

    • Author(s)
      Meng, Qi、鈴木里沙、小栗莉奈、 渡辺優子、辰川英樹、橋本寿史、人見清隆
    • Organizer
      小型魚類研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] タンパク質の架橋による翻訳後修飾反応を介した組織線維化の分子メカニズムの解析2019

    • Author(s)
      辰川英樹、人見清隆
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 胚線維化におけるタンパク質架橋化酵素の病態生理学的意義の解析2019

    • Author(s)
      竹内大修、辰川英樹、人見清隆
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 表皮立体培養細胞系を用いた タンパク質架橋化酵素群の機能解析2019

    • Author(s)
      加藤まなみ、手島裕文、栗林美樹、山口央輝、辰川英樹、人見清隆
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Studies on epidermal differentiation by air-liquid interface stimulation in three-dimensional culture2019

    • Author(s)
      手島裕文、栗林美樹、辰川英樹、人見清隆
    • Organizer
      日本研究皮膚科学会年次学術大会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Structural and Biochemical Investigation of amostatic Factor Fibrinogen Using Medaka (Oryzias lateipes)2019

    • Author(s)
      Qi Meng,、鈴木里沙、小栗莉奈、 渡辺優子、辰川英樹、橋本寿史、人見清隆
    • Organizer
      第42回日本分子生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] モデル生物としてのメダカを用いた組織型タンパク質架橋化酵素の機能解析2019

    • Author(s)
      渡邉優子、鈴木里沙、Meng Qi,辰川英樹、人見清隆
    • Organizer
      2019年度日本農芸化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 最終分化に空気暴露を必須とするヒト表皮立体培養細胞の性状解析2019

    • Author(s)
      手島裕文、栗林美樹、辰川英樹、人見清隆
    • Organizer
      2019年度日本農芸化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Isozyme-Specific Global Identification and Analysis of Transglutaminase Substrates in Fibrotic Diseases2018

    • Author(s)
      辰川英樹、人見清隆
    • Organizer
      ゴードン国際会議2018Transglutaminases in Human Disease Processes
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activation and Substrates of Transglutaminases2018

    • Author(s)
      人見清隆
    • Organizer
      ゴードン国際会議2018Transglutaminases in Human Disease Processes
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection and Identification of Possible Transglutaminase Substrates in the Mouse Renal Glomeruli.2018

    • Author(s)
      伊藤辰将、辰川英樹、山口央輝、高橋和男、人見清隆、湯澤 由紀夫
    • Organizer
      ゴードン国際会議2018Transglutaminases in Human Disease Processes
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immunochemical characterization of medaka orthologues for human thrombin2018

    • Author(s)
      鈴木里沙、渡邉優子、Meng Qi、辰川英樹、人見清隆
    • Organizer
      24th Japanese medaka and zebrafish meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] Biochemical characterization and analysis on gene-modified mutants of mammalian tissue-type transglutaminase orthologue in medaka2018

    • Author(s)
      渡邉優子、奥谷冬穂、鈴木里沙、Meng Qi、人見清隆 他4名
    • Organizer
      24th Japanese medaka and zebrafish meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] Biochemical characterization and establishment of gene-deficient medaka for transglutaminases, enzyme for cross-linking modification of proteins2018

    • Author(s)
      渡邉優子、鈴木里沙、Meng Qi、辰川英樹、亀井保博、橋本寿史、人見清隆
    • Organizer
      24th Japanese medaka and zebrafish meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎線維化において活性化するタンパク質架橋化酵素の役割りと基質タンパク質群の網羅的同定・解析2018

    • Author(s)
      辰川英樹、人見清隆
    • Organizer
      第9回分子腎臓フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎糸球体におけるタンパク質架橋接着酵素 (Transglutaminase 2) の基質候補探索と同定2018

    • Author(s)
      伊藤辰将、辰川英樹、山口央輝、高橋和男、人見清隆、湯澤 由紀夫
    • Organizer
      第9回分子腎臓フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Global Identification of Crosslinked Potential Tissue Transglutaminase Substrates in the Mouse Glomeruli2018

    • Author(s)
      伊藤辰将、辰川英樹、山口央輝、高橋和男、人見清隆、湯澤 由紀夫
    • Organizer
      第43回日本医療マススペクトル学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Isozyme-specific identification and characterization of substrates crosslinked by transglutaminases in liver fibrosis2018

    • Author(s)
      辰川英樹、人見清隆
    • Organizer
      The 13th International Symposium on ALPD and Cirrhosis
    • Related Report
      2018 Annual Research Report
  • [Presentation] タンパク質架橋化酵素による表皮構造タンパク質の修飾がバリア機能を強化する2018

    • Author(s)
      人見清隆
    • Organizer
      第91回日本生化学会大会シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝線維症において架橋される新規基質タンパク質の解析2018

    • Author(s)
      中川晴加、辰川英樹、人見清隆
    • Organizer
      2018年度日本農芸化学会中部支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] メダカのタンパク質架橋酵素群の機能解析と疾患モデルとしての変異体2018

    • Author(s)
      渡邉優子、鈴木里沙、Meng Qi, 辰川英樹、人見清隆
    • Organizer
      第4回ゼブラフィッシュメダカ創薬研究会
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi