A novel mechanism to regulate chronic inflammation through metabolic remodeling in obesity and senescence

• Project/Area Number: 17K08879
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Mie University
• Principal Investigator: OGATA Masato 三重大学, 医学系研究科, 教授 (60224094)
• Co-Investigator(Kenkyū-buntansha): 竹林 慎一郎 三重大学, 生物資源学研究科, 准教授 (50392022) ; 大隈 貞嗣 三重大学, 医学系研究科, 助教 (70444429)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性炎症 / 代謝症候群 / 細胞老化 / MAPキナーゼ / エピゲノム / 遺伝子改変マウス / 免疫学

Outline of Final Research Achievements

It is well established that the chronic inflammation is implicated in many diseases such as metabolic syndrome and cancer. However, the precise mechanism of the chronic inflammation has not been clarified yet. We have found that the chronic inflammation signaling cascade is involved in the development of type I diabetes and the accelerated aging in mouse models. Furthermore, we have demonstrated that the senescence of cells results in the metabolic remodeling which can induce the epigenetic modifications of proinflammatory cytokine genes and thus, can affect the senescence-associated secretory phenotype.

Academic Significance and Societal Importance of the Research Achievements

慢性炎症は多くの疾患と関わることから、それを生じる機構の解明は病態の理解や治療に欠かせない。本研究結果は、細胞老化によって生じる代謝リモデリングから遺伝子発現変化に至る分子機構を明らかにすることで、生活習慣病やがんの促進因子の理解と制御に役立つ。また、エピゲノム解析の目的で開発した新手法は、これまで困難であった単細胞での網羅的なゲノム構造変化を解析でき、本研究のみならず遺伝子の構造制御機構の解明にも有用である。

Research Products

• [Journal Article] Genome-wide Analysis of DNA Methylaton Identifies Differentially Methylated Loci Associated With Human Intervertebral Disc Degeneration. (2019)
  • Author(s): Ikuno A, Akeda K, Takebayashi S I, Shimaoka M, Okumura K, and Sudo A.
  • Journal Title: PLoS One Volume: 14 Issue: 9 Pages: e0222188-e0222188
  • DOI: 10.1371/journal.pone.0222188
  • Peer Reviewed / Open Access
• [Journal Article] Single-cell DNA Replication Profiling Identifies Spatiotemporal Developmental Dynamics of Chromosome Organization. (2019)
  • Author(s): Miura H, Takahashi S, Poonperm R, Tanigawa A, Takebayashi S I, and Hiratani I.
  • Journal Title: Nature Genetics Volume: 51 Issue: 9 Pages: 1356-1368
  • DOI: 10.1038/s41588-019-0474-z
  • Peer Reviewed / Open Access
• [Journal Article] Mapping mammalian replication domains using the ion torrent semiconductor sequencing platform (2018)
  • Author(s): Takebayashi Shin-ichiro、Ogata Shin、Ogata Masato、Okumura Katsuzumi
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 82 Issue: 12 Pages: 2098-2100
  • DOI: 10.1080/09168451.2018.1515617
  • Peer Reviewed
• [Journal Article] Correlation between Histone Acetylation and Expression of Notch1 in Human Lung Carcinoma and Its Possible Role in Combined Small Cell Lung Carcinoma. (2017)
  • Author(s): Hassan, W., Takebayashi, S. I., Abdalla, M. O., Fujino, K., Kudoh, S., Motooka, Y., Sato, Y., Naito, Y., Higaki, K., Wakimoto, J., Okada, S., Nakao, M., Ishikawa, Y., and Ito, T.
  • Journal Title: Lab. Invest. Volume: 印刷中 Issue: 8 Pages: 913-921
  • DOI: 10.1038/labinvest.2017.36
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anatomy of Mammalian Replication Domains. (2017)
  • Author(s): Takebayashi, S., Ogata, M., and Okumura, K.
  • Journal Title: Genes (Basel) Volume: 8 Issue: 4 Pages: 110-110
  • DOI: 10.3390/genes8040110
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice (2017)
  • Author(s): Shiokawa Moe、Lu Xiuyuan、Miyake Yasunobu、Ishikawa Eri、Pages Gilles、Pouyssegur Jacques、Ogata Masato、Yamasaki Sho
  • Journal Title: International Immunology Volume: 29 Issue: 10 Pages: 479-485
  • DOI: 10.1093/intimm/dxx056
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The role of metabolic activity of senescent cells in controlling cytokine gene expression (2018)
  • Author(s): Shin-ichiro Takebayashi, Sadatsugu Ookuma, and Masato Ogata
  • Organizer: 第47回日本免疫学会学術集会
• [Presentation] 哺乳類染色体複製ドメイン構造を単一細胞レベルで解析できるscRepli-seq法の開発 (2017)
  • Author(s): 竹林慎一郎、柴田隆豊、高橋沙央里、三浦尚、平谷伊智朗、奥村克純、緒方正人
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Mapping replication domains genome-wide in single mammalian cells (2017)
  • Author(s): Shin-ichiro Takebayashi, Takahiro Shibata, Saori Takahashi, Hisashi Miura, Ichiro Hiratani, Katsuzumi Okumura, Masato Ogata
  • Organizer: Gordon Research Conference