Analysis of the regulatory mechanism of macrophages involved in homeostasis by the transcription factor MafB

• Project/Area Number: 19K07499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Hamada Michito 筑波大学, 医学医療系, 准教授 (20567630)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: MAFB / マクロファージ / 恒常性 / 脾臓 / 恒常性維持 / MafB

Outline of Research at the Start

単球-マクロファージは組織修復や免疫恒常性維持に必要であり、慢性的な障害などでこれ らの機能が損なわれるとマクロファージ自体が病的要因となる。動脈硬化や心筋梗塞、腫瘍 ではマクロファージの組織修復機能が逆に病態を悪化させてしまうことがある。これらの病 巣に浸潤する単球のほとんどは脾臓由来であることが近年明らかになり、このメカニズムが 新たな治療ターゲットとして注目されている。本研究課題では転写因子MafBが脾臓での単 球-マクロファージの産生に必要であることを示し、マクロファージが関わる様々な病態の 新たな治療標的を探索することを目的とし研究を行う。

Outline of Final Research Achievements

Monocytes-macrophages are necessary for tissue repair and maintenance of immune homeostasis, and when these functions are impaired by chronic disorders, macrophages themselves become a pathological factor. In atherosclerosis, myocardial infarction, and tumors, the tissue repair function of macrophages may inversely aggravate the disease state. It has recently become clear that most of the monocytes infiltrating these lesions originate from the spleen, and this mechanism is attracting attention as a new therapeutic target. In this research project, we will demonstrate that the transcription factor MafB is required for the production of monocytes-macrophages in the spleen, and conduct research with the aim of searching for new therapeutic targets for various macrophage-associated pathologies.

Academic Significance and Societal Importance of the Research Achievements

本研究は脾臓から病変部や組織に浸潤するマクロファージ数を決定するメカニズムが脾臓マクロファージにあることを明らかにするという点で独自性、創造性が高いと考えている。このメカニズムが明らかとなり、転写因子MAFBの発現をコントロールすることによりマクロファージ数を制御することができれば、腫瘍だけではなく、心筋梗塞、急性腎障害などマクロファージが関わる疾患に対して効果を持つ、これまでにない薬剤の開発に役立つものと思われる

Research Products

• [Journal Article] Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs (2021)
  • Author(s): Jeon Hyojung、Asano Keigo、Wakimoto Arata、Kulathunga Kaushalya、Tran Mai Thi Nhu、Nakamura Megumi、Yokomizo Tomomasa、Hamada Michito、Takahashi Satoru
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 4374-4374
  • DOI: 10.1038/s41598-021-83652-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of MafB in macrophages (2020)
  • Author(s): Hamada Michito、Tsunakawa Yuki、Jeon Hyojung、Yadav Manoj Kumar、Takahashi Satoru
  • Journal Title: Experimental Animals Volume: 69 Issue: 1 Pages: 1-10
  • DOI: 10.1538/expanim.19-0076
  • NAID: 130007791547
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] Transcription factor MafB is a marker of tumor-associated macrophages in both mouse and humans (2020)
  • Author(s): Yadav Manoj Kumar、Inoue Yuri、Nakane-Otani Aya、Tsunakawa Yuki、Jeon Hyojung、Samir Omar、Teramoto Akari、Kulathunga Kaushalya、Kusakabe Manabu、Nakamura Megumi、Kudo Takashi、Takahashi Satoru、Hamada Michito
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 521 Issue: 3 Pages: 590-595
  • DOI: 10.1016/j.bbrc.2019.10.125
  • Peer Reviewed
• [Journal Article] Mice Lacking Core 1-derived O-glycan in Podocytes Develop Transient Proteinuria, Resulting in Focal Segmental Glomerulosclerosis (2020)
  • Author(s): Sayaka Fuseya, Riku Suzuki, Risa Okada, Kozue Hagiwara, Takashi Sato, Hisashi Narimatsu , Hideki Yokoi, Masato Kasahara, Toshiaki Usui , Naoki Morito, Kunihiro Yamagata, Takashi Kudo , Satoru Takahashi
  • Journal Title: Biochem Biophys Res Commun Volume: 523 Issue: 2 Pages: 1007-1013
  • DOI: 10.1016/j.bbrc.2019.12.033
  • Peer Reviewed
• [Presentation] 創傷治癒における転写因子MafBの機能解析 (2019)
  • Author(s): 井上由理; 濱田, 理人; 綱川祐貴; 高橋智
  • Organizer: 第42回 日本分子生物学会年
• [Presentation] Identifying the function of MafB expressed in macrophages during wound healing (2019)
  • Author(s): 井上由理; 濱田, 理人; 綱川祐貴; 高橋智
  • Organizer: Tsukuba conference
  • Int'l Joint Research