Molecular mechanisms of the association between .t2DM and Tskotudo

• Project/Area Number: 24390194
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Gunma University
• Principal Investigator: KURABAYASHI Masahiko 群馬大学, 医学(系)研究科(研究院), 教授 (00215047)
• Co-Investigator(Kenkyū-buntansha): ISO Tatsuya 群馬大学, 大学院医学系研究科, 准教授 (10400756)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 血管石灰化 / 血管平滑筋細胞 / リン / Klotho / オステオプロテジェリン / FABP / 交感神経 / CKD / カテコラミン / FGF23 / 慢性腎臓病 / 骨芽細胞 / 遺伝子 / 転写因子

Outline of Final Research Achievements

Both clinical and basic research demonstrated conflicting evidence regarding the pathophysiological role of Fibroblast growth factor 23 (FGF23) concentration in vascular calcification. We determine the effects of FGF23 on the osteoblastic gene expression in vascular smooth muscle cells (VSMC). HASMC transduced with adenovirus expressing human FGF23 (Ad-FGF23) exhibited a significant decrease in the expression of the osteoblast-marker genes. Of note, Ad-FGF23 increased mRNA and protein levels for osteoprotegerin (OPG), and human OPG promoter was activated by FGF23. FGF23 up-regulated OPG expression, whereas depletion of Klotho by siRNA attenuated FGF23-induced OPG expression. These results indicate that FGF23 suppresses osteoblastic gene expression and induces OPG expression in HASMC, and support the hypothesis that FGF23 counteracts the osteogenic conversion of vascular SMC as a component of compensatory mechanisms to mitigate the vascular calcification.

Research Products

• [Journal Article] Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure. (2015)
  • Author(s): Kasama S, Toyama T, Funada R, Takama N, Koitabashi N, Ichikawa S, Suzuki Y, Matsumoto N, Sato Y, Kurabayashi M
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 42 Pages: 761-70
  • Peer Reviewed
• [Journal Article] Fatty Acid Binding Protein 4 and 5 Play a Crucial Role in Thermogenesis under the Conditions of Fasting and Cold Stress. (2014)
  • Author(s): Syamsunarno MR, Iso T, Yamaguchi A, Hanaoka H, Putri M, Obokata M, Sunaga H, Koitabashi N, Matsui H, Maeda K, Endo K, Tsushima Y, Yokoyama T, Kurabayashi M.
  • Journal Title: PLoS ONE Volume: 9
  • Peer Reviewed
• [Journal Article] Hydrogen sulfide: a new regulator of osteoclastogenesis? (2014)
  • Author(s): Kurabayashi M.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 34 Pages: 471-3
  • Peer Reviewed
• [Journal Article] Hydrogen sulfide: a new regulator of osteoclastogenesis (2014)
  • Author(s): Kurabayashi M
  • Journal Title: Artherioscler Thromb Vasc Biol. Volume: 34 Pages: 471-473
  • Peer Reviewed
• [Journal Article] Palmitic Acid Induces Osteoblastic Differentiation in Vascular Smooth Muscle Cells through ACSL3 and NF-κB, Novel Targets of Eicosapentaenoic acid (2013)
  • Author(s): Kageyama A, Matsui H, 他7名
  • Journal Title: PLoS One Volume: 8(6) Issue: 6 Pages: e68197-e68197
  • DOI: 10.1371/journal.pone.0068197
  • Peer Reviewed
• [Journal Article] Capillary endothelial Fatty Acid binding proteins 4 and 5 play a critical role in Fatty Acid uptake in heart and skeletal muscle. (2013)
  • Author(s): Iso T, Maeda K, Hanaoka H, Suga T, Goto K, Syamsunarno MR, Hishiki T, Nagahata Y, Matsui H, Arai M, Yamaguchi A, Abumrad NA, Sano M, Suematsu M, Endo K, Hotamisligil GS, Kurabayashi M.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 33 Pages: 2549-2557
• [Journal Article] Stearoyl-CoA Desaturase-1 (SCD1) Augments Saturated Fatty Acid-Induced Lipid Accumulation and Inhibits Apoptosis in Cardiac Myocytes (2012)
  • Author(s): Matsui H, Yokoyama H, et al.
  • Journal Title: PLoS ONE Volume: 7
  • Peer Reviewed
• [Journal Article] Runx2/Smad3 Complex Negatively Regulates TGF-β-Induced Connective Tissue Growth Factor gene Expression in Vascular Smooth Muscle Cells (2012)
  • Author(s): Ohyama Yoshiaki, Kurabayashi Masahiko
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 19 Issue: 1 Pages: 23-35
  • DOI: 10.5551/jat.9753
  • NAID: 130004721900
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Azelnidipine inhibits Msx2-dependent osteogenic differentiation and matrix mineralization of vascular smooth muscle cells. (2012)
  • Author(s): Shimizu T, Tanaka T, I so T,
  • Journal Title: Int Heart J Volume: 53 Pages: 331-5
  • Peer Reviewed
• [Presentation] Early Increase in Circulating Fatty Acid Binding Protein 4 Levels in Patients with Acute Myocardial Infarction: Lipolysis as a novel marker for myocardial ischemia (2015)
  • Author(s): Masaru Obokata, Yoshiaki Ohyama, Hiroaki Sunaga, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: Japanese Circulation Society Annual Meeting
  • Place of Presentation: Osaka International Convention Center, 10F, 1008
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] Deletion of Fatty Acid Binding Protein 4/5 Exacerbate Cardiac Dysfunction Due to Insufficient ATP Production during Pressure Overload in Mice (2015)
  • Author(s): Mas R.A.A Syamsunarno, HIroki Matsui, Hiroaki Sunaga, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: Japanese Circulation Society Annual Meeting
  • Place of Presentation: Osaka International Convention Center
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] Fatty Acid-Binding Protein 5 as a Marker for Acute Myocardial Infarction (2015)
  • Author(s): Obokata, Yoshiaki Ohyama, Hiroaki Sunaga, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: Japanese Circulation Society Annual Meeting
  • Place of Presentation: RIHGA Royal Hotel Osaka West Wing
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] Immediate Administration of Selective Aldosterone Blocker Eplerenone Improves Sympathetic Nerve Activity after Reperfusion Therapy in Patients with Acute Myocardial Infarction (2015)
  • Author(s): Shu Kasama, Masahiko Kurabayashi
  • Organizer: Japanese Circulation Society Annual Meeting
  • Place of Presentation: Grand Front Osaka North Building Tower
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] Evidence for a protective role of FGF23 against vascular calcification (2014)
  • Author(s): Takehiro Nakahara
  • Organizer: 日本循環器学会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Molecular Mechanisms of vascular calcification (2014)
  • Author(s): Masahiko Kurabayashi
  • Organizer: International Vascular Biology Meeting 2014
  • Place of Presentation: みやこメッセ
  • Invited
• [Presentation] 心血管系の石灰化と心不全 (2012)
  • Author(s): Masahiko Kurabayashi
  • Organizer: 第16回日本心不全学会
  • Place of Presentation: 仙台
  • Year and Date: 2012-12-02
• [Presentation] Fibroblast Growth Factor 23 Inhibits Osteogenic Differentiation of Vascular Smooth Muscle Cells : A Protective Role against Vascular Calcification (2012)
  • Author(s): Nakahara T, KOwase K, et al.
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2012-03-17