The molecular mechanism by which transcriptional factor DEC1 modulates circadian rhythms of blood pressure.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390423
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: KATO Yukio 広島大学, 医歯薬保健学研究院, 研究員 (10112062)
• Co-Investigator(Kenkyū-buntansha): NOSHIRO Mitsuhide 広島大学, 医歯薬保健学研究院, 准教授 (00144858) ; KAWAMOTO Takeshi 広島大学, 医歯薬保健学研究院, 助教 (50224861) ; FUJIMOTO Katsumi 広島大学, 医歯薬保健学研究院, 助教 (40294566)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 転写因子 / ノックアウトマウス / 血圧 / 時計遺伝子 / DEC1

Research Abstract

Blood pressure shows a circadian variation, and many patients with cardiovascular diseases show disturbance in blood pressure circadian rhythm. We found that clock protein DEC1 binds and represses the E-boxes in the promoter of Atp1b1 gene, which encodes the beta subunit of Na/K-ATPase, whereas CLOCK activates these E-boxes. Consequently, the Atp1b1 mRNA and protein levels in the cardiovascular system showed circadian rhythms. Dec1-deficient mice showed decreased blood pressure, whereas clock-mutant mice showed increased blood pressure, as Na/K-ATPase is essential for the control of blood pressure. These findings revealed for the first time the molecular mechanism involved in blood pressure circadian rhythm.

Research Products

• [Journal Article] Seeding of mesenchymal stem cells into inner part of interconnected porous biodegradable scaffold by a new method with a filter paper (2014)
  • Author(s): Yamanaka K, Yamamoto K, Sakai Y, Suda Y, Shigemitsu Y, Kaneko T, Kato K, Kumagai T, Kato Y
  • Journal Title: Dental Materials Journal Volume: (in press)
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• [Journal Article] A novel protein, CHRONO, functions as a core component of the mammalian circadian clock (2014)
  • Author(s): Goriki A, Hatanaka F, Myung J, Kim J, Yoritaka T, Tanoue S, Fujimoto K, Kato Y, MatsubaraA, ForgerD, Takumi T
  • Journal Title: PLoS Biol Volume: 12(4) Pages: e1001839
  • DOI: 10.1371/journal.pbio.1001839.eCollection2014
  • Peer Reviewed
• [Journal Article] Different Circadian Expression of Major Matrix-Related Genes in Various Types of Cartilage : Modulation by Light-Dark Conditions (2013)
  • Author(s): Honda KK, Kawamoto T, Ueda HR, Nakashima A, Ueshima T, Yamada RG, Nishimura M, Oda R, Nakamura S, Kojima T, Noshiro M, Fujimoto K, Hashimoto S, Kato Y
  • Journal Title: J Biochem Volume: 154(4) Pages: 373-81
  • DOI: 10.1093/jb/mvt068
  • Peer Reviewed
• [Journal Article] Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stem cells expanded with fibroblast growth factor-2 (2013)
  • Author(s): Kanawa M, Igarashi A, Ronald VS, Higashi Y, Kurihara H, Sugiyama M, Saskianti T, Pan H, Kato Y
  • Journal Title: Cytotherapy Volume: 15(9) Pages: 1062-72
  • DOI: 10.1016/j.jcyt.2013.03.015
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 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, Masaki T
  • Journal Title: Kidney Int Volume: 84(2) Pages: 297-307
  • DOI: 10.1038/ki.2013.81
  • Peer Reviewed
• [Journal Article] Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model (2013)
  • Author(s): Mikami S, Nakashima A, Nakagawa K, Maruhashi T, Iwamoto Y, Kajikawa M, Matsumoto T, Kihara Y, Chayama K, Noma K, Ochi M, Nishimura M, Tsuji K, Kato Y, Goto C, Higashi Y
  • Journal Title: PLOS ONE Volume: 8(7) Pages: e67739
  • DOI: 10.1371/journal.pone.0067739
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• [Journal Article] ット変形性関節症モデルでの高分子ヒアルロン酸応答遺伝子の解析 (2013)
  • Author(s): 加藤幸夫, 本田清昌, 中島歩, 河本健
  • Journal Title: 臨床リウマチ Volume: 25(3) Pages: 174-184
• [Journal Article] The basic helix-loop-helix transcription factor DEC2 inhibits TGF-β-induced tumor progression in human pancreatic cancer BxPC-3 cells (2012)
  • Author(s): Sato F, Kawamura H, Wu Y, Sato H, Jin D, Bhawal UK, Kawamoto T, Fujimoto K, Noshiro M, Seino H, Morohashi S, Kato Y, Kijima H
  • Journal Title: Int J Mol Med Volume: 30(3) Pages: 495-501
  • DOI: 10.3892/ijmm.2012.1037
  • 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, Sato F, Yamada T, Bhawal UK, Kawamoto T, Fujimoto K, Noshiro M, Seino H, Morohashi S, Hakamada K, Abiko Y, Kato Y, Kijima H
  • Journal Title: Int J Oncol Volume: 41 Pages: 1337-1346
  • DOI: 10.3892/ijo.2012.1559
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• [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 UK, Kawamoto T, Fujimoto K, Noshiro M, Seino H, Morohashi S, Kato Y, Kijima H
  • Journal Title: Biomed Res Volume: 33(2) Pages: 75-82
  • DOI: 10.2220/biomedres.33.75
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• [Journal Article] Feasibility and limitations of the round robin test for assessment of in vitro chondrogenesis evaluation protocol in a tissue-engineered medical product (2012)
  • Author(s): Yokoi M, Hattori K, Narikawa K, Ohgushi H, Tadokoro M, Hoshi K, Takato T, Myoui A, Nanno K, Kato Y, Kanawa M, Sugawara K, Kobo T, Ushida T
  • Journal Title: J Tissue Eng Regen Med Volume: 6(7) Pages: 550-8
  • DOI: 10.1002/term.460
  • 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, Noshiro M, Kawamoto T, Nakashima A, Honda K, Fukuzaki-Dohi U, Honma S, Fujimoto K, Tanimoto K, Tanne K, Kato Y
  • Journal Title: Genes to Cells Volume: 17 Pages: 109-121
  • DOI: 10.1111/j.1365-2443.2011.01574.x
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• [Journal Article] The effect of synthetic octacalcium phosphate in a collagen scaffold on the osteogenicity of mesenchymal stem cells (2011)
  • Author(s): Kawai T, Anada T, Masuda T, Honda Y, Sakai Y, Kato Y, Kamakura S, Echigo S, Suzuki O
  • Journal Title: European Cells and Materials Volume: 22 Pages: 124-136
  • 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 Dev Volume: 20(9) Pages: 1539-47
  • DOI: 10.1089/scd.2010.0279
  • Peer Reviewed
• [Journal Article] PERIOD1 (PER1) has anti-apoptotic effects, and PER3 has pro-apoptotic effects during cisplatin (CDDP) treatment in human gingival cancer CA9-22 cells (2011)
  • Author(s): Sato F, Wu Y, Bhawal UK, Liu Y, Imaizumi T, Morohashi S, Kato Y, Kijima H
  • Journal Title: Eur J Cancer Volume: 47(11) Pages: 1747-58
  • DOI: 10.1016/j.ejca.2011.02.025
  • Peer Reviewed
• [Journal Article] Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1 (2011)
  • Author(s): Bhawal UK, 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) Pages: 420-9
  • DOI: 10.1002/path.2878
  • 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, Bhawal UK, Kawamoto T, Fujimoto K, Noshiro M, Morohashi S, Kato Y, Kijima H
  • Journal Title: Int J Mol Med Volume: 27(4) Pages: 491-5
  • DOI: 10.3892/ijmm.2011.617
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cell-induced cranial suture-like gap in rats (2011)
  • Author(s): Kaku M, Tai M, Kawata T, Fujita T, Motokawa M, Ohtani J, Sakai Y, Kato Y, Tanne K
  • Journal Title: Plast Reconstr Surg Volume: 127(1) Pages: 69-77
  • DOI: 10.1097/PRS.0b013e3181f95849
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• [Journal Article] 無血清で増幅した間葉系幹細胞と歯髄細胞 (2011)
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  • Journal Title: 広島歯科医学雑誌 Volume: 39(1) Pages: 1-8
• [Presentation] Isolation and expansion of mesenchymal stem cells from various tissues, including the umbilical cord, under serum-free conditions (2013)
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  • Organizer: Asia CORD
  • Place of Presentation: in Kobe, Japan
  • Year and Date: 20130419-20
• [Presentation] 無血清で作製した他家ヒト滑膜MSC(TEC)への期待 (2013)
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  • Place of Presentation: 横浜市
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• [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)
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  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 20120914-16
• [Presentation] Chemical Optimization of Both Culture Surfaces and Media Markedly Enhances MSC Proliferation (2012)
  • Author(s): Yukio Kato, Tania Saskianti, Masami Kanawa, Takeshi Kawamoto, Koichi Kato, Isao Hirata
  • Organizer: ISSCR Annual Meeting
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] 各組織由来MSC の均質性と細胞表面マーカーの発現に及ぼす無血清培地(STK 培地)の影響 (2012)
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  • Organizer: 第11回日本再生医療学会
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• [Presentation] 無血清培地(STK 系列培地)を用いた間葉系幹細胞からのTissue Engineered Construct(TEC)作成 (2012)
  • Author(s): 邵金昌, 長谷川森一, 杉田憲彦, 森口悠, 下村和範, 原真依子, 桂由紀, 坂井将典, 河原裕美, 弓削類, 加藤幸夫, 辻紘一郎, 吉川秀樹, 中村憲正
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  • Year and Date: 20120612-14
• [Presentation] Enhanced Proliferation of Stem Cells from Deciduous Teeth in Serum-free Media (2012)
  • Author(s): Noriko Goto, Katsumi Fujimoto, Shin-ichi Hasegawa, Kazuko Kitayama, Veronica Sainik Ronald, Katsuyuki Kozai, Yukio Kato
  • Organizer: STK1/STK2 8th Biennial Conference PDAA(Pediatric Dentistry Association of Asia)
  • Place of Presentation: Bali , Indonesia
  • Year and Date: 20120524-26
• [Presentation] 培養環境全体の化学的規定化による移植用間葉系幹細胞の増殖, 分化の促進 (2012)
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  • Organizer: (公)新化学技術推進協会ライフサイエンス技術部会・材料分科会
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• [Presentation] 膝関節症とヒアルロン酸への期待 (2012)
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  • Organizer: 第2回TOKYOヘルスコレクション
  • Place of Presentation: 東京都
  • Year and Date: 2012-03-15
• [Presentation] 再生医療用細胞(MSC など)の培養条件の完全化学規定化/至適化 (2012)
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  • Organizer: 第11回再生医療の実用化に関するニーズ発表会
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  • Year and Date: 2012-02-24
• [Presentation] Serum-Free Cultures for Human Mesenchymal Stem Cells using Defined Culture Surfaces (2011)
  • Author(s): Yukio Kato
  • Organizer: 1st Meeting of Surabaya Regenerative Medicine and Stem Cell Centre (SRMSC), 2nd Meeting of Indonesia Association of Tissue Bank (IATB), SYMPOSIUM
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  • Year and Date: 20110922-23
• [Presentation] 核内受容体ROR α 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, 能城光秀, 河本健, 福崎麗, 藤本勝巳, 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
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• [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)
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  • Organizer: 第52回日本生化学会中国・四国支部例会
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  • Year and Date: 20110513-14
• [Presentation] 間葉系幹細胞の軟骨分化におけるDEC2 の役割 (2011)
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• [Presentation] Identification of HMGA2 and SIM2 interaction in MSC (2011)
  • Author(s): Tania Saskianti, Takeshi Kawamoto , Yukio Kato
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  • Place of Presentation: 広島市
  • Year and Date: 20110128-30
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  • Year and Date: 20110128-30
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  • Author(s): Takeshi Kawamoto, Hiroshi Kubo, Tomoyuki Iwata, Katsumi Fujimoto, Mitsuhide Noshiro, Yukio Kato
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• [Book] DEC1/STRA13/SHARP2 and DEC2/SHARP1 coordinate physiological processes, including circadian rhythms in response to environmental stimuli. bHLH Factors in Development and Disease : Current topics in developmental biology (2014)
  • Author(s): Kato Y, Kawamoto T, Fujimoto K, Noshiro M
  • Publisher: Elsevier(in press)
• [Book] 幹細胞用無血清培地の開発, 幹細胞医療の実用化技術と産業展望 第3章幹細胞の維持培養と分化誘導 (2013)
  • Author(s): 加藤幸夫, 邵金昌, 長谷川森一, 西村正宏, 桂由紀, 中村憲正, 辻紘一郎
  • Total Pages: 293(50-60)
  • Publisher: (株)シーエムシー出版刊