Development and Molecular regulatory mechanism of mesenchymal epithelial transition (MET) model

• Project/Area Number: 16K20189
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: TAKAO Tomoka 慶應義塾大学, 医学部(信濃町), 特任助教 (40612429)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: MET / Wnt/β-catenin / 間葉系幹細胞 / 間葉-上皮転換 / METモデル / 上皮プロモーター

Outline of Final Research Achievements

Recently, mesenchymal-epithelial transition (MET) has been involved in many important life phenomena such as tissue and organ formation but not known in this detailed mechanism. Our previous results were shown that mesenchymal stem cells express epithelial-like markers in conditioned culture or in mouse transplantation models. In this study, we aimed to construct a model that reproduces the MET in vitro / in vivo and can be observed in real time. Epithelial-like cells could be reproduced in vivo, but did not reach modeling. However, we found that Raf-MEK or Wnt / β-catenin signaling may be involved in MET by drug researches. It is suggested that these results a foothold of the MET signal.

Academic Significance and Societal Importance of the Research Achievements

MET現象、特に成体内における自発的なMETについてはその全貌がほとんど明らかではない。この点に深く切り込んでいくという点で本研究は極めて独創的であると言えた。本研究の成果により既存薬を用いた薬剤研究によりMET制御機構と子宮内膜症はじめとする各種生体内MET機構を人為的に制御できる薬剤が見つかれば、新たなコンセプトの治療薬開発に繋がると期待される。

Research Products

• [Journal Article] The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats (2019)
  • Author(s): Miki Fumie、Maruyama Tetsuo、Miyazaki Kaoru、Takao Tomoka、Yoshimasa Yushi、Katakura Satomi、Hihara Hanako、Uchida Sayaka、Masuda Hirotaka、Uchida Hiroshi、Nagai Toshihiro、Shibata Shinsuke、Tanaka Mamoru
  • Journal Title: Biology of Reproduction Volume: - Issue: 5 Pages: 1215-1227
  • DOI: 10.1093/biolre/ioz004
  • Peer Reviewed / Open Access
• [Presentation] P2RY is involved in the migration and invasion of human extravillous trophoblast. (2019)
  • Author(s): Tetsuo Maruyama, Satomi Katakura, Tomoka Takao, Toru Arase, Yushi Yoshimasa, Shoko Tomisato, Sayaka Uchida, Hirotaka Masuda, Hiroshi Uchida, Mamoru Tanaka
  • Organizer: Society for Reproductive Investigation 66th Annual Scientific Meeting（SRI2019)
  • Int'l Joint Research
• [Presentation] Attempts to establish screening system for identification of drugs targeting human uterine endometrial cancer stem-like cells. (2018)
  • Author(s): Tetsuo Maruyama, Tomoka Takao, Hirotaka Masuda, Fumie Miki, Sayaka Uchida, Hiroshi Uchida, Mamoru Tanaka
  • Organizer: nternational Society for Stem Cell Research 2018 annual meeting (ISSCR2018)
  • Int'l Joint Research
• [Presentation] 子宮内膜幹細胞と上皮間葉転換をターゲットとした非内分泌的な子宮内膜症の新規治療． (2018)
  • Author(s): 升田博隆，古谷正敬，丸山哲夫，高尾知佳，内田 浩，内田明花，吉政佑之．片倉慧美，吉村泰典，片渕秀隆，田中 守
  • Organizer: 第23回日本生殖内分泌学会
• [Presentation] ヒト正常子宮平滑筋細胞に対する子宮筋腫関連遺伝子MED12の変異導入による機能的病因解析． (2018)
  • Author(s): 高尾知佳，丸山哲夫，内田 浩，内田明花，三木史恵，片倉慧美，吉政佑之，富里祥子，升田博隆，田中 守
  • Organizer: 第23回日本生殖内分泌学会
• [Presentation] 子宮体癌細胞の幹様細胞とそれを治療標的とする既存薬の探索． (2018)
  • Author(s): 高尾知佳，升田博隆，三木史恵，片倉慧美，吉政佑之，富里祥子，内田明花，内田 浩，田中 守，丸山哲夫
  • Organizer: 第41回日本分子生物学会
• [Presentation] Extravillous trophoblastの新しいマーカーとしてのG蛋白共役型受容体P2RY14とその細胞浸潤における役割． (2018)
  • Author(s): 片倉慧美，丸山哲夫，高尾知佳，瀬田康弘，吉政佑之，富里祥子，三木史恵，内田明花，升田博隆，内田 浩，田中 守，青木大輔
  • Organizer: 第70回日本産科婦人科学会
• [Presentation] CRISPR/CAS9システムによりMED12変異を導入したヒト子宮筋腫モデルの開発の試み． (2018)
  • Author(s): 高尾知佳，丸山哲夫，小野政徳，内田 浩，升田博隆，内田明花，三木史恵，片倉慧美，吉政佑之，藤原 浩，田中 守，青木大輔
  • Organizer: 第70回日本産科婦人科学会
• [Presentation] Anovel approach to treat emdometriosis via targeting epithelial-mesenchymal transition. (2018)
  • Author(s): Hirotaka Masuda, Masataka Furuya, Tetsuo Maruyama, Fumie Miki, Satomi Katakura, Yushi Yoshimasa, Sayaka Uchida, Hiroshi Uchida, Tomoka Takao, Hidetaka Katabuchi, Mamoru Tanaka, Daisuke Aoki
  • Organizer: 第70回日本産科婦人科学会