Mechanisms and physiological functions of intercellular communication by cell death

• Project/Area Number: 16H06385
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Miura Masayuki 東京大学, 大学院薬学系研究科(薬学部), 教授 (50202338)
• Project Period (FY): 2016-05-31 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥183,170,000 (Direct Cost: ¥140,900,000、Indirect Cost: ¥42,270,000); Fiscal Year 2020: ¥35,100,000 (Direct Cost: ¥27,000,000、Indirect Cost: ¥8,100,000); Fiscal Year 2019: ¥38,090,000 (Direct Cost: ¥29,300,000、Indirect Cost: ¥8,790,000); Fiscal Year 2018: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000); Fiscal Year 2017: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000); Fiscal Year 2016: ¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
• Keywords: 細胞死 / シグナルセンター / 組織連関 / カスパーゼ / ショウジョウバエ / 分泌 / 細胞間コミュニケーション

Outline of Final Research Achievements

Cell death triggers not only local response but also affects beyond the damaged tissue to systemically support tissue homeostasis. This phenomena is called SDR: Systemic Damage Response. The key to the SDR is that dead cells in the injured tissue release signaling molecules to surrounding cells and tissues, triggering a series of responses. This study revealed the mechanism of tissue homeostasis by SDR using genetics and biochemistry.

Academic Significance and Societal Importance of the Research Achievements

細胞死は従来不要な細胞の除去という消極的な生命現象と考えられていたが、生理的あるいは病態でおこる細胞死が積極的に周辺組織に働きかけ恒常性維持に関わる現象と分子メカニズムはその理解が遅れていた。本研究では個体レベルで発生や、組織再生、成体幹細胞の維持機構に関するSDRの分子機構を明らかにした。

Assessment Rating

Verification Result (Rating)

A

Research Products

• [Journal Article] Kynurenine Metabolism in the Fat Body Non-autonomously Regulates Imaginal Disc Repair in Drosophila (2020)
  • Author(s): Kashio Soshiro、Miura Masayuki
  • Journal Title: iScience Volume: 23 Issue: 12 Pages: 101738-101738
  • DOI: 10.1016/j.isci.2020.101738
  • Peer Reviewed / Open Access
• [Journal Article] Apoptosis is involved in maintaining the character of the midbrain and the diencephalon roof plate after neural tube closure (2020)
  • Author(s): Matsumoto, Y. Yamaguchi, Y. Hamachi, M. Nonomura, K. Muramatsu, Y. Yoshida, H. Miura, M.
  • Journal Title: Dev Biol Volume: 468 Issue: 1-2 Pages: 101-109
  • DOI: 10.1016/j.ydbio.2020.09.015
  • Peer Reviewed
• [Journal Article] ROS Regulate Caspase-Dependent Cell Delamination without Apoptosis in the Drosophila Pupal Notum (2020)
  • Author(s): Fujisawa Yuya、Shinoda Natsuki、Chihara Takahiro、Miura Masayuki
  • Journal Title: iScience Volume: 23 Issue: 8 Pages: 101413-101413
  • DOI: 10.1016/j.isci.2020.101413
  • Peer Reviewed / Open Access
• [Journal Article] Local Necrotic Cells Trigger Systemic Immune Activation via Gut Microbiome Dysbiosis in Drosophila (2020)
  • Author(s): Kosakamoto Hina、Yamauchi Toshitaka、Akuzawa-Tokita Yoriko、Nishimura Kei、Soga Tomoyoshi、Murakami Takumi、Mori Hiroshi、Yamamoto Kyosuke、Miyazaki Ryo、Koto Akiko、Miura Masayuki、Obata Fumiaki
  • Journal Title: Cell Reports Volume: 32 Issue: 3 Pages: 107938-107938
  • DOI: 10.1016/j.celrep.2020.107938
  • Peer Reviewed / Open Access
• [Journal Article] Diphthamide modification of eEF2 is required for gut tumor‐like hyperplasia induced by oncogenic Ras (2020)
  • Author(s): Tsuda‐Sakurai Kayoko、Kimura Masaki、Miura Masayuki
  • Journal Title: Genes to Cells Volume: 25 Issue: 2 Pages: 76-85
  • DOI: 10.1111/gtc.12742
  • Peer Reviewed
• [Journal Article] Dronc-independent basal executioner caspase activity sustains Drosophila imaginal tissue growth (2019)
  • Author(s): Shinoda N, Hanawa N, Chihara T, Koto A, Miura M
  • Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Volume: 116 Issue: 41 Pages: 20539-20544
  • DOI: 10.1073/pnas.1904647116
  • Peer Reviewed / Open Access
• [Journal Article] Temporal regulation of Lin28a during mammalian neurulation contributes to neonatal body size control. (2019)
  • Author(s): Miyazawa, H., Muramatsu, Y., Makino, H., Yamaguchi, Y., and Miura, M.
  • Journal Title: Dev. Dyn. Volume: 248 Issue: 10 Pages: 931-941
  • DOI: 10.1002/dvdy.87
  • Peer Reviewed
• [Journal Article] A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain. (2019)
  • Author(s): Polykratis, A., Marten, A., Onur Eren, R., Shirasaki, Y., Yamagishi, M., Yamaguchi, Y., Uemura, S., Miura, M., Holzmann, B., Kollias, G., Armaka, M., van Loo, G., Pasparakis, M.
  • Journal Title: Nature Cell Biol. Volume: 21 Issue: 6 Pages: 731-742
  • DOI: 10.1038/s41556-019-0324-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Non-apoptotic function of Drosophila caspase activation in epithelial thorax closure and wound healing (2019)
  • Author(s): Yuya Fujisawa, Hina Kosakamoto, Takahiro Chihara and Masayuki Miura
  • Journal Title: Development Volume: 146(4) Issue: 4 Pages: 1-28
  • DOI: 10.1242/dev.169037
  • Peer Reviewed / Open Access
• [Journal Article] A FRET biosensor for necroptosis uncovers two different modes of the release of DAMPs. (2018)
  • Author(s): Murai S, Yamaguchi Y, Shirasaki Y, Yamagishi M, Shindo R, Hildebrand JM, Miura R, Nakabayashi O, Totsuka M, Tomida T, Adachi-Akahane S, Uemura S, Silke J, Yagita H, Miura M, Nakano H
  • Journal Title: Nat Commun Volume: 9 Issue: 1 Pages: 4457-4457
  • DOI: 10.1038/s41467-018-06985-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mammalian embryos show metabolic plasticity toward the surrounding environment during neural tube closure. (2018)
  • Author(s): Miyazawa H, Yamamoto M, Yamaguchi Y, Miura M.
  • Journal Title: Genes to Cells Volume: 23 Issue: 9 Pages: 794-802
  • DOI: 10.1111/gtc.12626
  • Peer Reviewed / Open Access
• [Journal Article] Caspases and matrix metalloproteases facilitate collective behavior of non-neural ectoderm after hindbrain neuropore closure. (2018)
  • Author(s): Shinotsuka N, Yamaguchi Y, Nakazato K, Matsumoto Y, Mochizuki A, Miura M.
  • Journal Title: BMC Developmental Biology Volume: 18 Issue: 1 Pages: 17-17
  • DOI: 10.1186/s12861-018-0175-3
  • NAID: 120006528261
  • Peer Reviewed / Open Access
• [Journal Article] Nutritional control of stem cell division through S-adenosylmethionine in Drosophila intestine. (2018)
  • Author(s): Obata, F., Tsuda-Sakurai, K., Yamazaki, T., Nishio, R., Nishimura, K., Kimura, M., Funakoshi, M., and Miura, M.
  • Journal Title: Dev. Cell Volume: 44 Issue: 6 Pages: 741-751
  • DOI: 10.1016/j.devcel.2018.02.017
  • Peer Reviewed / Open Access
• [Journal Article] Dendritic Eph organizes dendrodendritic segregation in discrete olfactory map formation in Drosophila (2017)
  • Author(s): Marie Anzo, Sayaka Sekine, Shirin Makihara, Kinhong Chao, Masayuki Miura and Takahiro Chihara
  • Journal Title: Genes and Development Volume: 31 Issue: 10 Pages: 1054-1065
  • DOI: 10.1101/gad.297424.117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching (2017)
  • Author(s): Miyazawa, H., Yamaguchi, Y., Sugiura, Y., Honda, K., Kondo, K., Matsuda, F., Yamamoto, T., Suematsu, M., and Miura, M
  • Journal Title: Development Volume: 144 Issue: 1 Pages: 63-73
  • DOI: 10.1242/dev.138545
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] How tissue damage MET metabolism: Regulation of the systemic damage response. (2017)
  • Author(s): Kashio, S., Obata, F., and Miura, M.
  • Journal Title: Fly (Austin) Volume: Jan 2;11(1) Issue: 1 Pages: 27-36
  • DOI: 10.1080/19336934.2016.1221549
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Drosophila SETDB1 and caspase cooperatively fine-tune cell fate determination of sensory organ precursor. (2016)
  • Author(s): Shinoda, N., Obata, F., Zhang, L., and Miura, M
  • Journal Title: Genes to Cells Volume: 21 Issue: 4 Pages: 378-386
  • DOI: 10.1111/gtc.12348
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses. (2016)
  • Author(s): Sakuma C, Saito Y, Umehara T, Kamimura K, Maeda N, Mosca TJ, Miura M, Chihara T.
  • Journal Title: Cell Rep Volume: 16 Issue: 9 Pages: 2289-2297
  • DOI: 10.1016/j.celrep.2016.07.066
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] カスパーゼの多彩な生理機能と制御 (2021)
  • Author(s): 三浦正幸
  • Organizer: 千里ライフサイエンスセミナー“細胞死研究の新展開"
  • Invited
• [Presentation] Caspase regulates epithelial fusion during development (2019)
  • Author(s): Miura, M.
  • Organizer: The Batsheva de Rothschild Seminar on Non-apoptotic roles of apoptotic proteins
• [Presentation] ショウジョウバエ上皮融合でのカスパーゼ機能 (2019)
  • Author(s): 三浦正幸
  • Organizer: 第92回日本生化学会シンポジウム
• [Presentation] Nutritional control of tissue damage and homeostasis. (2018)
  • Author(s): Miura, M.
  • Organizer: Australia-Japan Meeting on Cell Death. Plenary lecture
  • Int'l Joint Research / Invited
• [Presentation] Cell life and death interactions in organisms. (2018)
  • Author(s): Miura, M.
  • Organizer: The 13th Japanese Drosophila Research Conference. Plenary lecture
  • Invited
• [Presentation] 発生時の上皮融合で見られる細胞の排除機構 (2018)
  • Author(s): 三浦正幸
  • Organizer: 第91回日本生化学会大会シンポジウム
• [Presentation] カスパーゼの生体機能 (2017)
  • Author(s): 三浦正幸
  • Organizer: 第26回日本Cell Death学会学術集会特別講演
  • Invited
• [Presentation] 組織傷害に応じた全身性の代謝応答 (2017)
  • Author(s): 三浦正幸
  • Organizer: 第5回がんと代謝研究会
  • Invited
• [Presentation] 組織傷害を起点とした全身性代謝応答とその生理機能 (2017)
  • Author(s): 三浦正幸
  • Organizer: 第14回レドックス・ライフイノベーションシンポジウム
  • Invited
• [Presentation] カスパーゼによる上皮形成安定化機構 (2017)
  • Author(s): 三浦正幸
  • Organizer: ConBio2017ワークショップ
  • Invited
• [Presentation] Biology of cell destruction: active roles of cell death in development and organismal homeostasis. (2017)
  • Author(s): Miura, M.
  • Organizer: The 17th RIKEN Center for Developmental Biology Lecture.
  • Int'l Joint Research / Invited
• [Presentation] Coordination of cell death and proliferation in tissue quorum control. Symposium in New biological principles emerged from cell-cell communications. (2016)
  • Author(s): Miura, M.
  • Organizer: The 68th Annual Meeting of the Japan Society for Cell Biology
  • Invited
• [Presentation] Systemic damage response through S-adenosyl-methionine metabolism. (2016)
  • Author(s): Miura, M.
  • Organizer: International Symposium “Pharmacology of 7TM-receptors and downstream signaling pathways”
  • Int'l Joint Research / Invited
• [Presentation] Metabolic control of tissue repair and homeostasis in Drosophila. (2016)
  • Author(s): Miura, M.
  • Organizer: International Symposium ”Cell competition, apoptosis and cancer”
  • Int'l Joint Research / Invited
• [Remarks] 遺伝学ホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~genetics/index.html