Regulation of Prox1-mediated lymphatic differentiation ofendothelial cells by transcriptional regulators

• Project/Area Number: 19570176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: The University of Tokyo
• Principal Investigator: WATABE Tetsuro The University of Tokyo, 大学院・医学系研究科, 助教 (00334235)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 細胞分化 / 血管 / リンパ管 / ES細胞 / 再生医療 / 癌

Research Abstract

リンパ管は生体内の恒常性の維持など生理的に重要な役割を担っているとともに悪性腫瘍の転移などの病的状態にも関与している。本研究においてはProx1を中心とした転写因子のネットワークによるリンパ管分化の制御機構の包括的な解明を試みた。成果として血管内皮細胞がリンパ管内皮細胞へと分化する過程でProx1が重要な役割を果たすこと、そしてEts-2とCOUP-TFIIがリンパ管の形成と維持においてProx1と結合することにより、Prox1の機能をそれぞれ正と負の方向に調節していることが示された。

Research Products

• [Journal Article] TTF-1 inhibits TGF-βJournal of Cell Science.-mediatedepithelial-to-mesenchymal transition inlung adenocarcinoma cells (2009)
  • Author(s): Saito RA, Watabe T, Horiguchi K, KohyamaT, Saitoh M, Nagase T, Miyazono K.
  • Journal Title: Cancer Research 69 Pages: 2783-2791
  • Peer Reviewed
• [Journal Article] COUP-TFIIregulates the functions of Prox1 inlymphatic endothelial cells throughdirect interaction (2009)
  • Author(s): Yamazaki T, Yoshimatsu Y, Morishita Y, Miyazono K, Watabe T.
  • Journal Title: Genes to Cells 14 Pages: 425-434
  • Peer Reviewed
• [Journal Article] TTF-1 inhibits TGF-13-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. (2009)
  • Author(s): Saito RA, Watabe T, Horiguchi K, Kohyama T, Saitoh M, Nagase T, Miyazono K:
  • Journal Title: Cancer Research 69 Pages: 2783-2791
  • Peer Reviewed
• [Journal Article] COUP-TFII regulates the functions of Proxl in lymphatic endothelial cells through direct interaction. (2009)
  • Author(s): Yamazaki T, Yoshimatsu Y, Morishita Y, Miyazono K, Watabe T
  • Journal Title: Genes to Cells 14 Pages: 425-434
  • Peer Reviewed
• [Journal Article] Snail isrequired for TGFβ-inducedendothelial-mesenchymal transition ofembryonic stem cell-derived endothelialcells (2008)
  • Author(s): Kokudo T, Suzuki Y, Yoshimatsu Y,Yamazaki T, Watabe T, Miyazono K.
  • Journal Title: Journal of Cell Science.(* : correspondingauthor) 121 Pages: 3317-3324
  • Peer Reviewed
• [Journal Article] Development ofstabilin2+ endothelial cells from mouseembryonic stem cells by inhibition ofTGFβ/activin signaling (2008)
  • Author(s): Nonaka H, Watabe T, Saito S, Miyazono K, Miyajima A.
  • Journal Title: Biochemical and Biophysical Research Communications 375 Pages: 256-260
  • Peer Reviewed
• [Journal Article] Ras signaling directsendothelial specification of VEGFR2+vascular progenitor cells (2008)
  • Author(s): Kawasaki K, Watabe T, Sase H, HirashimaM, Koide H, Morishita Y, Yuki K, SasaokaT, Suda T, Katsuki M, Miyazono K, Miyazawa K
  • Journal Title: Journal ofCell Biology 181 Pages: 131-141
  • Peer Reviewed
• [Journal Article] Inhibition ofendogenous TGF-β signaling enhanceslymphangiogenesis (2008)
  • Author(s): Oka M, Iwata C, Suzuki H, Kiyono K, Morishita Y, Watabe T, Komuro A, Kano MR, Miyazono K
  • Journal Title: Blood 111 Pages: 4571-4579
  • Peer Reviewed
• [Journal Article] BMPs promoteproliferation and migration ofendothelial cells via stimulation ofVEGF-A/VEGFR2 and Angiopoietin-1/Tie2signals (2008)
  • Author(s): Suzuki Y, Montagne K, Nishihara A, Watabe T, Miyazono K
  • Journal Title: Journal of Biochemistry(* : corresponding author) 143 Pages: 199-206
  • Peer Reviewed
• [Journal Article] Deletion of PSCA increases metastasis ofTRAMP-induced prostate tumors withoutaltering primary tumor formation (2008)
  • Author(s): Moore ML, Teitell MA, Kim Y, Watabe T, Reiter RE, Witte ON, Dubey P
  • Journal Title: Prostate 68 Pages: 139-151
  • Peer Reviewed
• [Journal Article] Snail is required for TGFβ-induced endothelial-mesenchymal transition of embryonic, stem cell-derived endothelial cells. (2008)
  • Author(s): Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Watabe T. Miyazono
  • Journal Title: Journal of Cell Science 121 Pages: 3317-3324
  • Peer Reviewed
• [Journal Article] Development of stabilin2+ endothelial cells from mouse embryonic stemcells by inhibition of TGFβ/activin signaling. (2008)
  • Author(s): Nonaka H, Watabe T, Saito S, Miyazono K, Miyajima A
  • Journal Title: Biochemical and Biophysical Research Communications 375 Pages: 56-260
  • Peer Reviewed
• [Journal Article] Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells (2008)
  • Author(s): Kawasaki K, Watabe T, Sase H, Hirashima M, Koide H, Morishita Y, Yuki K, Sasaoka T, Suda T, Katsuki M, Miyazono K, Miyazawa K.
  • Journal Title: Journal of Cell Biology 181 Pages: 131-141
  • Peer Reviewed
• [Journal Article] Inhibition of endogenous TGF-13 signaling enhances lymphangiogenesis (2008)
  • Author(s): Oka M, Iwata C, Suzuki H, Kiyono K, Morishita Y, Watabe T, Komuro A, Kano MR, Miyaono K.
  • Journal Title: Blood 111 Pages: 4571-4579
  • Peer Reviewed
• [Journal Article] BMPs promote proliferation and migration of endothelial cells via stimulation of VEGF-ANEGFR2 and Angiopoietin-1/Tie2 signals. (2008)
  • Author(s): Suzuki Y, Montagne K, Nishihara A, Watabe T, Miyazono K.
  • Journal Title: Journal of Biochemistry 143 Pages: 199-206
  • Peer Reviewed
• [Journal Article] BMPs promote proliferation and migratin of endothelial cells via stimulation of VEGF-A/VEGFR2 and Angiopoietin-1/Tie2 signals (2008)
  • Author(s): Suzuki Y, Montagne K, Nishihara A, Watabe T, Miyazono K.
  • Journal Title: Journal of Biochemistry 143 Pages: 199-206
  • Peer Reviewed
• [Journal Article] Inhibition of endogenous TGF-β signaling enhances lymphangiogensis (2008)
  • Author(s): Oka M, Iwata C, Suzuki H, kiyono K, Morishita Y, Watabe T, Komuro A, Kano MR, Miyazono K
  • Journal Title: Blood (印刷中)(掲載確定)
  • Peer Reviewed
• [Journal Article] Proxlinduces lymphatic endothelialdifferentiation via integrin α9 andother signaling cascades (2007)
  • Author(s): Mishima K, Watabe T, Saito A, YoshimatsuY, Imaizumi N, Masui S, Hirashima M, Morisada T, Oike Y, Araie M, Niwa H, KuboH, Suda T, Miyazono K.
  • Journal Title: MolecularBiology of the Cell 18 Pages: 1421-1429
  • Peer Reviewed
• [Journal Article] Activin-Nodal signaling is involved inpropagation of mouse embryonic stemcells (2007)
  • Author(s): Ogawa K, Saito A, Matsui H, Suzuki H,Ohtsuka S, Shimosato D, Morishita Y, Watabe T, Niwa H, Miyazono K.
  • Journal Title: Journal of Cell Science 120 Pages: 55-65
  • Peer Reviewed
• [Journal Article] Proxl induces Iymphatic endothelial differentiation via integrin α9 and other signaling casca (2007)
  • Author(s): Mishima K, Watabe T, Saito A, Yoshimatsu Y, Imaizumi N, Masui S, Hirashima M, Morisada T, Oike Y, Araie M, Niwa H, Kubo H, Suda T, Miyazono K
  • Journal Title: Molecular Biology of the Cell 18 Pages: 1421-1429
  • Peer Reviewed
• [Presentation] Snail is required forTGF-β-induced endothelial-mesenchymaltransition of embryonic stem cell-derivedendothelial cells (2008)
  • Author(s): Watabe T, Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Miyazono K.
  • Organizer: 第16回日本血管生物医学会
  • Place of Presentation: 金沢・石川県立音楽堂交流ホール
  • Year and Date: 2008-12-04
• [Presentation] Snail is required for TGF-β-inducedendothelial-mesenchymal transition ofembryonic stem cell-derived endothelialcells (2008)
  • Author(s): Watabe T, Kokudo T, Suzuki Y, YoshimatsuY, Yamazaki T, Mihira H, Miyazono K.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] Snail is required for TGF-β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2008)
  • Author(s): Watabe T, Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Mihira H, Miyazono K
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場、名古屋
  • Year and Date: 2008-10-28
• [Presentation] リンパ管発生における転写・シグナルネットワークの役割 (2008)
  • Author(s): 渡部徹郎
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 都市センターホテル、東京
  • Year and Date: 2008-07-09
• [Presentation] リンパ管発生における転写・シグナルネットワークの役割 (2008)
  • Author(s): 渡部徹郎
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 東京・都市センターホテル
  • Year and Date: 2008-07-08
• [Presentation] Roles of Etsfamily members in the regulation ofProxl-mediated lymphaticdifferentiation of endothelial cells (2008)
  • Author(s): Watabe T, Yoshimatsu Y, Yamazaki T, Morikawa M, Miyazono K.
  • Organizer: The 15^<th> International Vascular BiologyMeeting
  • Place of Presentation: Sydney Convention, Exhibition Centre, Sydney, Australia
  • Year and Date: 2008-06-04
• [Presentation] Roles of Ets family members in the regulation of Proxl-mediated lymphatic differentiation of endothelial cells. (2008)
  • Author(s): Watabe T, Yoshimatsu Y, Yamazaki T, Morikawa M, Miyazono K.
  • Organizer: The 15th International Vascular Biology Meeting
  • Place of Presentation: Sydney Convention & Exhibition Centre, Sydney, Australia
  • Year and Date: 2008-06-04
• [Presentation] Regulation of Prox1-mediated lymphaticdifferentiation of endothelial cells bytranscriptional regulators (2008)
  • Author(s): Watabe, T., Yoshimatsu, Y., Yamazaki, T., Morikawa, M., Miyazono, K.
  • Organizer: TheU.S. -Japan Cooperative Cancer Research Program Workshop
  • Place of Presentation: 京都・京都ガーデンパレス
  • Year and Date: 2008-03-20
• [Presentation] Regulation of Prox1-mediated lymphatic differentiation of endothelial cells by transcriptional regulators (2008)
  • Author(s): Watabe, T., Yoshimatsu, Y., Yamazaki, T., Morikawa, M., and Miyazono, K.
  • Organizer: The U.S.-Japan Cooperative Cancer Resarch Program Workshop
  • Place of Presentation: 京都
  • Year and Date: 2008-03-20
• [Presentation] Snail is required for TGF-β-inducedendothelial-mesenchymal transition ofembryonic stem cell-derived endothelialcells (2008)
  • Author(s): Watabe T, Kokudo T, Suzuki Y, YoshimatsuY, Yamazaki T, Mihira H, Miyazono K.
  • Organizer: The 28^<th> Sapporo Cancer SeminarInternational Symposium"TGF-βsignaling and cancer"
  • Place of Presentation: 札幌・北海道大学 学術交流会館大講堂
• [Presentation] Snail is required for TGF-13-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2008)
  • Author(s): Watabe T, Kokudo T, Suzuki Y, Y oshimatsu Y, Yamazaki T, Mihira H, Miyazono K
  • Organizer: The 28th Sapporo Cancer Seminar International Symposium "TGF-β signaling and cancer"
  • Place of Presentation: 北海道大学学術交流会館大講堂、札幌
• [Presentation] Snail is required for TGF-β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells
  • Author(s): Watabe T, Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Mihira H, Miyazono K
  • Organizer: 第16回日本血管生物医学会