Cell Type-specific Role of TGFb Signaling in Cardiac Remodeling and Myocardial Energy Metabolism

• Project/Area Number: 25461101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Gunma University
• Principal Investigator: Koitabashi Norimichi 群馬大学, 医学部附属病院, 助教 (10420093)
• Co-Investigator(Kenkyū-buntansha): KURABAYASHI Masahiko 群馬大学, 医学部附属病院, 教授 (00215047)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 心臓リモデリング / サイトカイン / エネルギー代謝

Outline of Final Research Achievements

Hemodynamic stress induces cardiomyocyte hypertrophy and myocardial fibrosis, resulting pathological cardiac remodeling and heart failure. Myocardial energetics has been shown to be altered in the development of heart failure. How ever, its precise mechanism remains unclear. We hypothesized that TGF-b or BMP7 induced signaling would induce modifications in myocardial energetic abnormality associating with ATP depletion and hypoxic response. We created fibroblast-specific TGFb-receptor deletion model and examined stress-responses in heart. Myocardial fibrosis was inhibited in this model but no significant changes in cardiac function and myocardial energetics. On the other hand, endothelial-specific TGFb receptor deletion model showed no obvious phenotypic difference with control.

Research Products

• [Journal Article] Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway (2015)
  • Author(s): Araki S, Izumiya Y, Rokutanda T, Ianni A, Hanatani S, Kimura Y, Onoue Y, Senokuchi T, Yoshizawa T, Yasuda O, Koitabashi N, Kurabayashi M, Braun T, Bober E, Yamagata K, Ogawa H
  • Journal Title: Circulation Volume: 132(12) Issue: 12 Pages: 1081-1093
  • DOI: 10.1161/circulationaha.114.014821
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CD36 is indispensable for thermogenesis under conditions offasting and cold stress. (2015)
  • Author(s): Putri M, Syamsunarno MR, Iso T, Yamaguchi A, Hanaoka H, Sunaga H, Koitabashi N, Matsui H, Yamazaki C, Kameo S, Tsushima Y, Yokoyama T, Koyama H, Abumrad NA, Kurabayashi M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 457 Issue: 4 Pages: 520-525
  • DOI: 10.1016/j.bbrc.2014.12.124
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dynamic Gene Expression Patterns in Animal Models of Early and Late Heart Failure Reveal Biphasic Bidirectional Transcriptional Activation of Signaling Pathways. (2014)
  • Author(s): Rowell J, Koitabashi N, Kass DA, Barth AS
  • Journal Title: Physiol Genomics Volume: 46 Issue: 20 Pages: 779-787
  • DOI: 10.1152/physiolgenomics.00054.2014
  • 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, Matsui H, 他12名
  • Journal Title: PLoS ONE Volume: 9(3) Issue: 3 Pages: 90825-90825
  • DOI: 10.1371/journal.pone.0090825
  • Peer Reviewed / Open Access
• [Journal Article] Cardiomyocyte-Specific Transforming Growth Factor β Suppression Blocks Neutrophil Infiltration, Augments Multiple Cytoprotective Cascades, and Reduces Early Mortality After Myocardial Infarction. (2014)
  • Author(s): Rainer PP, Hao S, Vanhoutte D, Lee DI, Koitabashi N, Molkentin JD, Kass DA.
  • Journal Title: Circulation Research Volume: 114 Issue: 8 Pages: 1246-1257
  • DOI: 10.1161/circresaha.114.302653
  • Peer Reviewed
• [Journal Article] A critical role of fatty acid binding protein 4 and 5 (FABP4/5) in the systemic response to fasting (2013)
  • Author(s): Syamsunarno MR, Iso T, Hanaoka H, Yamaguchi A, Obokata M, Koitabashi N, Goto K, Hishiki T, Nagahata Y, Matsui H, Sano M, Kobayashi M, Kikuchi O, Sasaki T, Maeda K, Murakami M, Kitamura T, Suematsu M, Tsushima Y, Endo K, Hotamisligil GS, Kurabayashi M
  • Journal Title: PLoS One Volume: 14;8 Issue: 11 Pages: e79386-e79386
  • DOI: 10.1371/journal.pone.0079386
  • Peer Reviewed
• [Presentation] Inhibition of TGFb signaling in perivascular periostin expressiong cells attenuates the development of pulmonary arterial hypertension in mice (2015)
  • Author(s): Norimichi Koitabashi, Mitsuru Seki, Hirokazu Arakawa, Masahiko Kurabyashi
  • Organizer: 第32回国際心臓研究学会日本部会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-12-11
• [Presentation] Cardiac Energetics Re-evaluated by in vivo visualization of ATP levels (2015)
  • Author(s): Norimichi Koitabashi, Masamichi Yamamoto, Takayuki Musashi, Mai Samejima, Tatsuya Iso, Hiromi Imamura, Masahiko Kurabayashi
  • Organizer: 第19回日本心不全学会学術集会
  • Place of Presentation: グランフロント大阪
  • Year and Date: 2015-10-22
• [Presentation] Fibroblast-Specific TGFbeta Receptor Inhibition Promotes Smooth Muscle Proliferation in Coronary Artery of Pressure-overloaded Mouse Heart (2014)
  • Author(s): Norimichi Koitabashi
  • Organizer: 日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-10 – 2014-10-12