Elucidation of the molecular mechanisms by which endothelial cells transdifferentiate into mesenchymal cells

• Project/Area Number: 23701045
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIMATSU Yasuhiro 東京大学, 大学院・医学系研究科, 特任研究員 (60586684)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 血管内皮細胞 / がん関連線維芽細胞 / 内皮間葉分化転換 / TGF-ss / 腫瘍関連線維芽細胞 / VE-cadherin-Creマウス / TGF-β / 国際情報交流

Research Abstract

Endothelial-mesenchymal transition (EndMT) in which endothelial cells transdifferentiate into mesenchymal cells has been implicated in the malignant phenotypes of heart diseases and tumorigenesis in the human body. In this study, we elucidated the molecular mechanisms by which endothelial cells undergo EndMT. As a molecular mechanism for EndMT, we found that TGF-β, a representative EndMT-inducing cytokine, induces the expression of the mesenchymal marker Smooth Muscle Alpha-Actin through inducing the expression and the nuclear translocation of the transcription factor MRTF-A during EndMT in MS-1 endothelial cells.

Research Products

• [Journal Article] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2012)
  • Author(s): Mihira H
  • Journal Title: Journal of Biochemistry Volume: 151 Issue: 2 Pages: 145-156
  • DOI: 10.1093/jb/mvr121
  • Peer Reviewed
• [Journal Article] Roles of TGF-ss signals in endothelial- mesenchymal transition during cardiac fibrosis. (2011)
  • Author(s): Yasuhiro Yoshimatsu and TetsuroWatabe
  • Journal Title: International Journal of Inflammation 2011 Volume: - Pages: 724080-724080
  • DOI: 10.4061/2011/724080
  • Peer Reviewed
• [Presentation] Roles of signaling and transcriptionalnetworks during TGF-β-induced endothelial-to-mesenchymal transition (2013)
  • Author(s): Tetsuro Watabe, Yasuhiro Yoshimatsu et al.
  • Organizer: The 9th AACR-JCA joint conference
  • Place of Presentation: Maui, HI, U.S.A.
  • Year and Date: 2013-02-24
• [Presentation] FGF signals inhibit the TGF-β-inducedendothelial-to-mesenchymal transition (2012)
  • Author(s): Yuichi Akatsu, Yasuhiro Yoshimatsu et al.
  • Organizer: 第20回日本血管生物医学会学術総会
  • Place of Presentation: 徳島、徳島県郷土文化会館
  • Year and Date: 2012-12-07
• [Presentation] Activation of signaling and transcriptional networks during TGF-β-induced endothelial- mesenchymal transition (2012)
  • Author(s): Tetsuro Watabe, Yasuhiro Yoshimatsu et al.
  • Organizer: International Vascular Biology Meeting2012
  • Place of Presentation: Wiesbaden,Germany
  • Year and Date: 2012-06-04
• [Presentation] In vitro and in vivo analysis ofmesenchymal cells originated by endothelial-mesenchymal transition (2012)
  • Author(s): Yuichi Akatsu, Yasuhiro Yoshimatsu et al.
  • Organizer: International Vascular Biology Meeting2012
  • Place of Presentation: Wiesbaden,Germany
  • Year and Date: 2012-06-04
• [Presentation] TGF-ss-induced mesenchymal transition ofMS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2011)
  • Author(s): Hajime Mihira, Yasuhiro Yoshimatsu et al.
  • Organizer: 第19回日本血管生物医学会学術総会
  • Place of Presentation: 東京, 東京ステーションコン ファレンス
  • Year and Date: 2011-12-08
• [Presentation] Activation of signaling and transcriptional networks during TGF-β-induced endothelial- mesenchymal transition (2011)
  • Author(s): Tetsuro Watabe, Yasuhiro Yoshimatsu et al.
  • Organizer: TGF-meeting in Uppsala
  • Place of Presentation: Ludwig Institute for Cancer Research, Uppsala, Sweden
  • Year and Date: 2011-08-17
• [Presentation] TGF-ss-induced mesenchymal transition ofMS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2011)
  • Author(s): Hajime Mihira, Yasuhiro Yoshimatsu et al.
  • Organizer: 第114回日本小児科学会学術集会
  • Place of Presentation: 東京,グランドプリンスホテル新高輪
  • Year and Date: 2011-08-12
• [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2011)
  • Author(s): Tetsuro Watabe
  • Organizer: TGF-β meeting in Uppsala
  • Place of Presentation: Ludwig Institute for Cancer Research, Uppsala, Sweden
• [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2011)
  • Author(s): Hajime Mihira
  • Organizer: 第114回日本小児科学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪, 東京都
• [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2011)
  • Author(s): Hajime Mihira
  • Organizer: 第19回日本血管生物医学会
  • Place of Presentation: 東京ステーションコンファレンス, 東京都
• [Presentation] Activation of signaling and transcriptional networks during TGF-β-induced endothelial-mesenchymal transition
  • Author(s): Tetsuro Watabe
  • Organizer: The 17th International Vascular Biology Meeting
  • Place of Presentation: Wiesbaden, Germany
• [Presentation] In vitro and in vivo analysis of mesenchymal cells originated by endothelial-mesenchymal transition
  • Author(s): Yuichi Akatsu
  • Organizer: The 17th International Vascular Biology Meeting
  • Place of Presentation: Wiesbaden, Germany
• [Presentation] FGF signals inhibit the TGF-β-induced endothelial-to-mesenchymal transition
  • Author(s): Yuichi Akatsu
  • Organizer: 第20回日本血管生物医学会学術集会
  • Place of Presentation: 徳島県（徳島県郷土文化会館）
• [Presentation] Roles of signaling and transcriptional networks during TGF-β-induced endothelial-to-mesenchymal transition
  • Author(s): Tetsuro Watabe
  • Organizer: The 9th AACR-JCA joint conference
  • Place of Presentation: Maui, HI, USA
• [Book] 血管生物医学事典 (2011)
  • Author(s): 佐藤靖史・森田育男・高倉伸幸・小室一成(監修者4名)
  • Publisher: 朝倉書店
• [Book] 血管生物医学事典 (2011)
  • Author(s): 佐藤靖史・森田育男・高倉伸幸・小室一成 (監修者4名)
  • Publisher: 朝倉書店