Impact of macrophage transcription factor MafB on cardiac remodeling after myocardial infarction.

• Project/Area Number: 26860541
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Yamagata University
• Principal Investigator: Hasegawa Hiromasa 山形大学, 医学部, 非常勤講師 (20715396)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マクロファージ / 心筋梗塞 / リモデリング / 転写因子MafB

Outline of Final Research Achievements

Transcription factor MafB is expressed only in monocytes and macrophages among hematopoietic cells, which plays a role in the terminal differentiation of macrophages. MafB knockout mice die immediately after birth due to developmental anomalies of neurons in the respiratory center. We generated transgenic mice that express dominant negative (DN) MafB capable of suppressing endogenous MafB transcription activity only in macrophages. MafB inhibition promotes macrophage apoptosis. Macrophage apoptosis plays a role in cardiac remodeling after myocardial infarction. We investigated macrophage apoptosis, efferocytosis, cytokine production and macrophage polarization using peritoneal macrophages of DN-MafB mice and MafB knockdown RAW264.7 cells. MafB inhibition promotes macrophage polarization to M1 and secretion of various inflammatory cytokines which cause inflammation and tissue disruptive reaction. There was no difference in effecrocytosis between DN-MafB and wild type macrophages.

Research Products

• [Journal Article] HECT‐Type Ubiquitin E3 Ligase ITCH Interacts With Thioredoxin‐Interacting Protein and Ameliorates Reactive Oxygen Species Induced Cardiotoxicity (2016)
  • Author(s): Yoichiro Otaki, Hiroki Takahashi, Tetsu Watanabe, Akira Funayama, Shunsuke Netsu, Yuki Honda, Taro Narumi, Shinpei Kadowaki, Hiromasa Hasegawa, Shintaro Honda, Takanori Arimoto, Tetsuro Shishido, Takuya Miyamoto, Hideaki Kamata, Osamu Nakajima, Isao Kubota
  • Journal Title: Am Heart Assoc. Volume: 5 Issue: 1
  • DOI: 10.1161/jaha.115.002485
  • Peer Reviewed / Open Access
• [Journal Article] High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis (2015)
  • Author(s): Narumi T, Shishido T, Otaki Y, Kadowaki S, Honda Y, Funayama A, Honda S, Hasegawa H, Kinoshita D, Yokoyama M, Nishiyama S, Takahashi H, Arimoto T, Miyamoto T, Watanabe T, Tanaka A, Woo C, Abe J, Takeishi Y, Kubota I
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 82 Pages: 1-12
  • DOI: 10.1016/j.yjmcc.2015.02.018
  • Peer Reviewed / Open Access / Int'l Joint Research