Molecular mechanisms of TGF-b signaling for reprogramming

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659146
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: ITOH Fumiko 東京薬科大学, 生命科学部, 准教授 (70502582)
• Project Period (FY): 2011 – 2012
• Keywords: iPS細胞 / 遺伝子改変マウス / TGF-ss / インヒビター / CAG-Cre

Research Abstract

It is required for the improvement and process of establishment efficiency induced pluripotent stem (iPS) cells. Reprogramming of the cells involves an intermediate mesenchymal-epithelial transition (MET)-like process that is also regulated by TGF ss In this study, we have tried to find out the molecularmechanisms in MET process regulated by TGF-ss. We used mouse embryonic fibroblast (MEF) cells from TGF-b receptors conditional knockout mice crossing with CAG-Cre Tg mice. Then we generated iPS cellsfrom the MEF cells by lentivirus vectors which encode Nakayama factors under the control of doxycycline dependent expression system. These iPS cells showed clonal variety and required longer passage for stabilization.

Research Products

• [Journal Article] Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions (2012)
  • Author(s): Itoh F, Itoh S, Adachi T, Ichikawa K, Matsumura Y, Takagi T, Festing T, Watababe T, Weinstein M, Karlsson S & Kato M
  • Journal Title: Blood Volume: 119 Pages: 5320-5328
• [Journal Article] Implication of TGF-ss as a survival for during tumor development (2012)
  • Author(s): Itoh S & Itoh F
  • Journal Title: J. Biochem Volume: 151 Pages: 559-562
• [Journal Article] Pathogenic involvement of heregulin-ss 1in anti-atherogenesis (2012)
  • Author(s): Watanabe T, Sato K, Itoh F, & Iso Y
  • Journal Title: Regul. Pept Volume: 175 Pages: 11-14
• [Journal Article] Endogenous bioactive peptides as potential biomarkers for atherosclerotic coronary heart disease (2012)
  • Author(s): Watanabe T, Sato K, Itoh F Wakabayashi K, Shichiri M, & Hirano T
  • Journal Title: Sensors (Basel) Volume: 12 Pages: 4974-4985
• [Journal Article] Interference of E2-2-mediated effect in endothelial cells by FAM96B through its limited expression of E2-2 (2011)
  • Author(s): Yang W, Itoh F, Ohya H, Kishimoto F, Tanaka A, Nakano N, Itoh S & Kato M
  • Journal Title: Cancer Sci Volume: 102(10) Pages: 1808-1814
• [Journal Article] Inhibitory machinery for the TGF-ss family signaling pathway (2011)
  • Author(s): Itoh F. & Itoh S
  • Journal Title: Growth Factors Volume: 29(5) Pages: 163-73
• [Presentation] TGF-ss signaling regulates lymphangiogenesis in vivo (2012)
  • Author(s): Ichikawa, K., Takahiro, T., Itoh, F., Itoh, S., Oliver, G., and Watanabe, T
  • Organizer: 10th Korea-Japan Joint Symposium on Vasuclar Biology
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 20121200
• [Presentation] TGF-ss signaling inhibit tumor angiogenesis in vivo (2012)
  • Author(s): Takagi, T., Ichikawa, K., Itoh, S., Fruttiger, M., Itoh, F., and Watanabe, T
  • Organizer: 10th Korea-Japan Joint Symposium on Vasuclar Biology
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 20121200
• [Presentation] Dicer-dependent miRNA pathway is important for vascular development (2012)
  • Author(s): Itoh, F., Hazome, S., Fruttiger, M., Itoh, S., and Watanabe, T
  • Organizer: 10th Korea-Japan Joint Symposium on Vasuclar Biology
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 20121200
• [Presentation] Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions (2012)
  • Author(s): Itoh, F
  • Organizer: 17th International Vascular Biology Meeting
  • Place of Presentation: Wiesbaden, Germany
  • Year and Date: 20120600
• [Presentation] TGF-ss signaling regulates lymphangiogenesis in mice development (2012)
  • Author(s): Itoh, F., Ichikawa, K., Itoh,S., Oliver,G., and Watanabe, T
  • Organizer: 17th International Vascular Biology Meeting
  • Place of Presentation: Wiesbaden, Germany
  • Year and Date: 20120600
• [Book] 血管新生と腫瘍血管、がんの増殖と悪性化の分子機構 (2012)
  • Author(s): 伊東史子、血管新生と腫瘍血管、宮澤恵二、伊東進編
  • Total Pages: 67-77
  • Publisher: 宮澤恵二、伊東進編
• [Patent(Industrial Property Rights)] ミオスタチン阻害ペプチド (2013)
  • Inventor(s): 林 良雄、伊東 史子 他
  • Industrial Property Rights Holder: 東京薬科大学
  • Industrial Property Number: 2013-17540
  • Filing Date: 2013-01-31