functional analysis of transcription factors which control multipotency of mesenchymal stem cells

• Project/Area Number: 22592068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: KAWAMOTO Takeshi 広島大学, 大学院・医歯薬保健学研究院, 助教 (50224861)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 間葉系幹細胞 / 細胞分化 / 転写因子 / 再生医療

Research Abstract

To analyze the function of mesenchymal stem cell-specific transcription factors, we performed overexpression and knockdown experiments of these factors. Knockdown of some transcription factors inhibited growth and osteogenic differentiation of mesenchymal stem cells. SIM2 seems to be the master gene in the cascade of transcriptional regulation in the stem cells. These results indicate that these transcription factors are involved int the growth and differentiation of mesenchymal stem cells.

Research Products

• [Journal Article] Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-beta1 signaling. (2013)
  • Author(s): Ueno, T., Nakashima, A., DOI:, S., Kawamoto, T., Honda, K., Yokoyama, Y., DOI:, T., Higashi, Y., Yorioka, N., Kato, Y., Kohno, N., and Masaki, T
  • Journal Title: Kidney Int Volume: 84(2) Issue: 2 Pages: 297-307
  • DOI: 10.1038/ki.2013.81
  • Peer Reviewed
• [Journal Article] The basic helix-loop-helix transcription factor DEC2 inhibits TGF-beta-induced tumor progression in human pancreatic cancer BxPC-3 cells (2012)
  • Author(s): Sato, F., Kawamura, H., Kawamoto, T., Noshiro, M.,(他10名)
  • Journal Title: Int J Mol Med Volume: 30 Issue: 3 Pages: 495-501
  • DOI: 10.3892/ijmm.2012.1037
  • Peer Reviewed
• [Journal Article] Smad3 and Snail show circadian expression in human gingival fibroblasts, human mesenchymal stem cell, and in mouse liver (2012)
  • Author(s): Sato, F., Wu, Y., Noshiro, M.
  • Journal Title: Biochem Biophys Res Commun Volume: 419 Issue: 2 Pages: 441-446
  • DOI: 10.1016/j.bbrc.2012.02.076
  • Peer Reviewed
• [Journal Article] Identification of a new clock-related element EL-box involved in circadian regulation by BMAL1/CLOCK and HES1 (2012)
  • Author(s): Ueshima, T., Kawamoto, T., Honda, K.K, Noshiro, M., Fujimoto, K., Nakao, S., Ichinose, N., Hashimoto, S., Gotoh, O., Kato, Y
  • Journal Title: Gene Volume: 510 (2) Issue: 2 Pages: 118-125
  • DOI: 10.1016/j.gene.2012.08.022
  • Peer Reviewed
• [Journal Article] BHLH transcription factor DEC2 regulates pro-apoptotic factor Bim in human oral cancer HSC-3 cells. Biomed Res (2012)
  • Author(s): Wu, Y., Sato, F., Bhawal, U.K., Kawamoto, T., Fujimoto, K., Noshiro, M., Seino, H., Morohashi, S., Kato, Y., and Kijima, H
  • Journal Title: Biomed Res. Volume: 33 Pages: 75-82
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22572381.
  • Peer Reviewed
• [Journal Article] The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer (2012)
  • Author(s): Wu, Y., Kawamoto, T., Noshiro, M., et al.(他10名)
  • Journal Title: Int J Oncol Volume: 41 Issue: 4 Pages: 1337-1346
  • DOI: 10.3892/ijo.2012.1559
  • Peer Reviewed
• [Journal Article] IL-1β-mediated up-regulation of DEC1 in human gingiva cells via the Akt (2012)
  • Author(s): Bhawal UK, Ito Y, Tanimoto K, Sato F, Fujimoto K, Kawamoto T, Sasahira T, Hamada N, Kuniyasu H, Arakawa H, Kato Y
  • Journal Title: J Cell Biochem Volume: Vol113 Issue: 10 Pages: 3246-53
  • DOI: 10.1002/jcb.24205
  • Peer Reviewed
• [Journal Article] Regulation of basic helix-loop-helix transcription factors Dec1 and Dec2 by RORα and their roles in adipogenesis. (2012)
  • Author(s): Ozaki N
  • Journal Title: Genes to Cells Volume: 17 Issue: 2 Pages: 107-121
  • DOI: 10.1111/j.1365-2443.2011.01574.x
  • Peer Reviewed
• [Journal Article] BHLH transcription factor DEC2 regulates pro-apoptotic factor Bim in human oral cancer HSC-3 cells (2012)
  • Author(s): Wu, Y., Sato, F., Bhawal, U.K., Kawamoto, T., Fujimoto, K., Noshiro, M., Seino, H., Morohashi, S., Kato, Y., Kijima, H
  • Journal Title: Biomedical Research Volume: 33 Issue: 2 Pages: 75-82
  • DOI: 10.2220/biomedres.33.75
  • NAID: 130004470811
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed
• [Journal Article] Smad3 and Snail show circadian expression in human gingival fibroblasts, human mesenchymal stem cell, and in mouse liver Corresponding (2012)
  • Author(s): Sato F, et al
  • Journal Title: BBRC Volume: (In press)
  • Peer Reviewed
• [Journal Article] BHLH transcription factor DEC2 regulates pro-apoptotic factor Bim in human oral cancer HSC-3 cells (2012)
  • Author(s): Wu Y, et al
  • Journal Title: Biomedical Research Volume: (In press)
  • Peer Reviewed
• [Journal Article] Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1. Bhawal (2011)
  • Author(s): U.K., Sato, F., Arakawa, Y., Fujimoto, K., Kawamoto, T., Tanimoto, K., Ito, Y., Sasahira, T., Sakurai, T., Kobayashi, M., Kashima, I., Kijima, H., Kuniyasu, H., Abiko, Y., Kato, Y., Sato, S
  • Journal Title: J. Pathol Volume: 224(3) Issue: 3 Pages: 420-429
  • DOI: 10.1002/path.2878
  • Peer Reviewed
• [Journal Article] Impact of Zinc Fingers and Homeoboxes 3 (ZHX3) on the Regulation of Mesenchymal Stem Cell Osteogenic Differentiation (2011)
  • Author(s): Suehiro F, Nishimura M, Kawamoto T, Kanawa M, Yoshizawa Y, Murata H, Kato Y
  • Journal Title: Stem Cells Develop Volume: 20(9) Issue: 9 Pages: 1539-1547
  • DOI: 10.1089/scd.2010.0279
  • Peer Reviewed
• [Journal Article] Basic helix-loop-helix transcription factors DEC1 and DEC2 regulate the paclitaxel-induced apoptotic pathway of MCF-7 human breast cancer cells (2011)
  • Author(s): Wu, Y., Sato, F., Kawamoto, T., Fujimoto, K., Noshiro, M., (他4名)
  • Journal Title: Int J Mol Med Volume: 27 Issue: 4 Pages: 491-495
  • DOI: 10.3892/ijmm.2011.617
  • Peer Reviewed
• [Journal Article] Impact of Zinc Fingers and Homeoboxes 3 (ZHX3) on the Regulation of Mesenchymal Stem Cell Osteogenic Differentiation. (2011)
  • Author(s): Suehiro F, Nishimura M, Kawamoto T, Kanawa M, et al.
  • Journal Title: Stem Cells Dev. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Anti-apoptotic effect of the basic helix-loop helix (bHLH) transcription factor DEC2 in human breast cancer cells (2010)
  • Author(s): Liu Y, Sato F, Kawamoto T, Fujimoto K, Morohashi S, et al.
  • Journal Title: Genes Cells Volume: 15 Pages: 315-325
  • Peer Reviewed
• [Journal Article] Roles of DEC1 and DEC2 in the core loop of the circadian clock, and clock outputs to metabolism. (2010)
  • Author(s): Kato Y, Noshiro M, Fujimoto K, Kawamoto T
  • Journal Title: Hirosaki Med.J. Volume: 61
  • Peer Reviewed
• [Journal Article] ENGLISH ASSISTANCE WITH CORPUS ANALYSIS --DICTIONARY, THESAURUS, COLLOCATIONS-- (2010)
  • Author(s): Ohtake H, Fujita N, Kawamoto T, Ugawa Y, Morren, B, et al.
  • Journal Title: IADIS International Conference e-Learning Pages: 285-288
  • Peer Reviewed
• [Presentation] 概日リズムを制御する新規時計エレメントEL-boxの同定 (2012)
  • Author(s): 河本健
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 郡山市
• [Presentation] Chemical Optimization of Both Culture Surfaces and Media Markedly Enhances MSC Proliferation (2012)
  • Author(s): Yukio Kato
  • Organizer: ISSCR Annual Meeting
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] 間葉系幹細胞の軟骨分化における DEC2の役割 (2011)
  • Author(s): 笹本智子、藤本勝巳、金輪真佐美、河本健、能城光秀、道田将彦、尾崎徳継、丹根一夫、加藤幸夫
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 間葉系幹細胞の増殖・分化ならびにインテクリン発現に対する転写因子 GATA6 の作用 (2011)
  • Author(s): 道田将彦、河本健、能城光秀、藤本勝巳、金輪真佐美、尾崎徳継、笹本智子、丹根一夫、加藤幸夫
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] Transcription factors regulating differentiation of MSC (2011)
  • Author(s): Kawamoto T., Kubo H., Iwata Y., Fujimoto K., Noshiro M., Kato Y.
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] Identification of HMGA2 and SIM2 interaction in MSC (2011)
  • Author(s): Saskianti T., Kawamoto T., Kato Y.
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] Expression profiles of nuclear receptors and their functions in rat growth plate Chondrocytes (2011)
  • Author(s): Ozaki N., Noshiro M., Honda K., Hayashibara K., Kawamoto T., Fujimoto K., Tanne K., Kato Y
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] DNA修復関連遺伝子の低酸素応答性転写抑制機構 (2011)
  • Author(s): 谷本圭司, 他
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸市
• [Presentation] 間葉系幹細胞の軟骨分化におけるDEC2の役割 (2011)
  • Author(s): 笹本智子, 他
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 開葉系幹細胞の増殖・分化ならびにインテクリン発現に対する転写因子GATA6の作用 (2011)
  • Author(s): 道田将彦, 他
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 核内受容体RORαによる時計遺伝子DEC1,DEC2の発現調節と脂肪分化 (2011)
  • Author(s): 尾崎徳継, 他
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] Inhibitory Effect of Mesenchymal Stem Cells on the Progression of Experimental Peritoneal Fibrosis in a Rat Model (2010)
  • Author(s): Ueno T., Nakashima A., Taniguchi Y., Kawamoto T., Kato Y., Yorioka N
  • Organizer: 3rd annual meeting of American Society of Nephrology
  • Place of Presentation: Denver, USA.
• [Presentation] 骨髄・滑膜由来間葉系幹細胞におけるインテグリン遺伝子発現への転写因子 GATA6 の作用 (2010)
  • Author(s): 道田 将彦、河本 健、久保 裕嗣、金輪 真佐美、丹根 一夫、加藤 幸夫
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口市
• [Presentation] Decl Regulates Circadian Variation of Blood Pressure (2010)
  • Author(s): Nakashima A, Kawamoto T, Noshiro M, Honda K, et al.
  • Organizer: 43rd annual meeting of American Society of Nephrology
  • Place of Presentation: Denver, USA
• [Presentation] Inhibitory Effect of Mesenchymal Stem Cells on the Progression of Experimental Peritoneal Fibrosis in a Rat Model (2010)
  • Author(s): Ueno T, Nakashima A, Taniguchi Y, Kawamoto T, et al.
  • Organizer: 43rd annual meeting of American Society of Nephrology
  • Place of Presentation: Denver, USA
• [Presentation] 血圧とNa/K-ATPaseの日内変動:Dec1による制御 (2010)
  • Author(s): 中島歩, 河本健, 加藤幸夫
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 核内受容体(RORα)とSREBP1cによるベーシック・ヘリックス・ループ・ヘリックス型転写因子(Dec1, Dec2)の発現調節と脂肪分化 (2010)
  • Author(s): 尾崎徳継, 能城光秀, 福崎麗, 河本健, 藤本勝己, 丹根一夫, 加藤幸夫
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 骨髄・滑膜由来間葉系幹細胞におけるインテグリン遺伝子発現への転写因子GATA6の作用 (2010)
  • Author(s): 道田将彦、河本健、久保裕嗣、金輪真佐美、丹根一夫、加藤幸夫
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口市
• [Patent(Industrial Property Rights)] 脂質代謝関連疾患の検査方法、ならびに脂質代謝関連疾患の予防および/または治療剤の評価方法 (2011)
  • Inventor(s): 加藤幸夫、河本健、藤本勝巳、能城光秀
  • Industrial Property Rights Holder: 広島大学
  • Industrial Property Number: 2011-022172
  • Filing Date: 2011-02-03
• [Patent(Industrial Property Rights)] 非ヒト動物、細胞、血圧調節物質の評価方法、血圧調節条件の評価方法および血圧の調節方法 (2010)
  • Inventor(s): 加藤幸夫、河本健、能城光秀、中島歩
  • Industrial Property Rights Holder: 広島大学
  • Industrial Property Number: 2010-236891
  • Filing Date: 2010-10-22