MafB regulate C1q genes in macrophage

• Project/Area Number: 25860205
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: University of Tsukuba
• Principal Investigator: Hamada Michito 筑波大学, 医学医療系, 助教 (20567630)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: マクロファージ / MafB / C1q / 自己免疫疾患 / アポトーシス

Outline of Final Research Achievements

Transcription factor MafB is specifically expressed in macrophages in hematopoietic cells. During the adult stage, both Mafb-deficient fetal liver cells that were transplanted into recipient mice and macrophage-specific Mafb conditional knock-out mice exhibited autoimmune phenotypes. Macrophage efferocytosis (apoptotic cells uptake) is important for inhibiting autoimmune disease. The efferocytosis ability of Mafb-deficient macrophages was strongly reduced. The expression of complement component-1q (C1q), which is known as the first protein in the classical complement pathway and for mediating efferocytosis, was reduced in Mafb-null macrophages. The promoter analysis of C1q genes showed that MafB directly regulates C1qa, C1qb, and C1qc promoter. Consistent with this result, the classical pathway was also decreased in Mafb-deficient mice analyzed by hemolysis assay. These results suggest that MafB primarily regulates C1q genes.

Research Products

• [Journal Article] MafB deficiency accelerates the development of obesity in mice (2016)
  • Author(s): Mai Thi Nhu Tran, Michito Hamada, Megumi Nakamura, Hyojung Jeon, Risa Kamei, Yuki Tsunakawa, Kaushalya Kulathunga, Yuan-Yu Lin, Kumiko Fujisawa, Takashi Kudo, Satoru Takahashi
  • Journal Title: FEBS openbio Volume: 印刷中 Issue: 6 Pages: 540-547
  • DOI: 10.1002/2211-5463.12058
  • NAID: 120007135330
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential expression patterns of MafB and c-Maf in macrophages in vivo and in vitro (2016)
  • Author(s): Dhouha Daassi, Michito Hamada , Hyojung Jeon, Yuki Imamura, Mai Thi Nhu Tran, Satoru Takahashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 473 Issue: 1 Pages: 118-124
  • DOI: 10.1016/j.bbrc.2016.03.063
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] <i>In Vivo</i> image Analysis Using iRFP Transgenic Mice (2014)
  • Author(s): Mai Thi Nhu Tran, Junko Tanaka, Michito Hamada, Yuka Sugiyama, Shota Sakaguchi, Megumi Nakamura, Satoru Takahashi, Yoshihiro Miwa
  • Journal Title: Experimental Animals Volume: 63 Issue: 3 Pages: 311-319
  • DOI: 10.1538/expanim.63.311
  • NAID: 130004677824
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] Sexually dimorphic expression of Mafb regulates masculinization of the embryonic urethral formation (2014)
  • Author(s): Suzuki K, Numata T, Suzuki H, Raga DD, Ipulana L, Yokoyama C, Matsushita S, Hamada M, Nakagata N, Nishinakamura R, Kume S, Takahashi S, and Yamada G.
  • Journal Title: PNAS Volume: 18;111(46) Issue: 46 Pages: 16407-12
  • DOI: 10.1073/pnas.1413273111
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Overexpression of Mafb in Podocytes Protects against Diabetic Nephropathy. (2014)
  • Author(s): Morito N, Yoh K, Ojima M, Okamura M, Nakamura M, Hamada M, Shimohata H, Moriguchi T, Yamagata K, Takahashi S.
  • Journal Title: J Am Soc Nephrol. Volume: 印刷中 Issue: 11 Pages: 2546-2557
  • DOI: 10.1681/asn.2013090993
  • Peer Reviewed / Open Access
• [Journal Article] Functions of the Large Maf Transcription Factors and Macrophages (2014)
  • Author(s): Michito Hamada, Satoru Takahashi
  • Journal Title: Macrophages: Biology and Role in the Pathology of Diseases Volume: 1 Pages: 509-517
  • DOI: 10.1007/978-1-4939-1311-4_25
  • ISBN: 9781493913107, 9781493913114
• [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis (2014)
  • Author(s): Michito Hamada, Megumi Nakamura, Mai Thi Nhu Tran, Takashi Moriguchi, Cynthia Hong, Takayuki Ohsumi, Tra Thi Huong Dinh, Manabu Kusakabe, Motochika Hattori, Tokio Katsumata, Satoko Arai, Katsuhiko Nakashima, Takashi Kudo, Etsushi Kuroda, Chien-Hui Wu, Pei-Han Kao, Masaharu Sakai, Hitoshi Shimano, Toru Miyazaki et al
  • Journal Title: Nature communications Volume: 5:3147 Pages: 1-14
  • Peer Reviewed
• [Presentation] Transcription factor MafB is indispensable for homeostatic function of macrophages (2016)
  • Author(s): Michito Hamada
  • Organizer: 第24回マクロファージ分子細胞生物学国際シンポジウム
  • Place of Presentation: 東京 ソラシティカンファレンスセンター
  • Year and Date: 2016-06-04
  • Int'l Joint Research / Invited
• [Presentation] MafBはマクロファージにおける恒常性維持機能に重要である (2015)
  • Author(s): 濱田 理人1、Mai Thi Nhu Tran1、浅野 圭吾1、中村 恵弥1、全 静孝1、工藤 崇、高橋 智
  • Organizer: BMB2015（第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会）
  • Place of Presentation: 兵庫 神戸ポートアイランド
  • Year and Date: 2015-12-01
  • Invited
• [Remarks] 動脈硬化の進行を促進するたんぱく質を発見
  • URL: https://www.tsukuba.ac.jp/attention-research/p201401201900.html
• [Remarks] プレスリリース
  • URL: http://www.tsukuba.ac.jp/wp-content/uploads/p201401201900.pdf