脂質メディエイターがつくる加齢微小環境の解析と治療への展開

• Project Area: Quality of lipids in biological systems
• Project/Area Number: 18H04673
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: Kyoto University
• Principal Investigator: 柳田 素子 京都大学, 医学研究科, 教授 (70378769)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: 老化 / 炎症 / 加齢微小環境

Outline of Annual Research Achievements

高齢者は腎障害に罹患しやすく、しかも回復しにくいが、その回復力低下のメカニズムは不明である。申請者は、加齢個体の腎臓内には「三次リンパ組織」が形成され、免疫応答の場となって炎症を遷延させることで、障害の修復を遅延させることを見出した。さらに、三次リンパ組織形成には、高齢腎の線維芽細胞が獲得する特殊な形質が重要であることを見いだしたが、その形質獲得の背景には、高齢腎における微小環境の変容が寄与しているのではないかと考えた。
申請者は、transcriptomeの結果、脂質代謝関連遺伝子が三次リンパ組織形成に伴って大きく変化していることを見出した。加えて、trascriptomeとlipidomicsの結果をあわせて解析し、いくつかの脂質メディエイターに注目し、その合成阻害薬を投与し、三次リンパ組織形成および腎障害がどのように変化するかを検討した。さらに三次リンパ組織を形成した腎臓のmass imagingを行い、さまざまな脂質の局在についても検討した。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Developmental stages of tertiary lymphoid tissue reflect local injury and inflammation in murine and human kidneys (2020)
  • Author(s): Yuki Sato, Peter Boor, Shingo Fukuma, Barbara M. Klinkhammer, Hironori Haga, Osamu Ogawa, Jurgen Floege and Motoko Yanagita
  • Journal Title: Kidney International Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional heterogeneity of resident fibroblasts in the kidney (2019)
  • Author(s): SATO Yuki、YANAGITA Motoko
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 95 Issue: 8 Pages: 468-478
  • DOI: 10.2183/pjab.95.033
  • NAID: 130007728132
  • ISSN: 0386-2208, 1349-2896
  • Year and Date: 2019-10-11
  • Peer Reviewed
• [Journal Article] Immunology of the ageing kidney (2019)
  • Author(s): Sato Yuki、Yanagita Motoko
  • Journal Title: Nature Reviews Nephrology Volume: 15 Issue: 10 Pages: 625-640
  • DOI: 10.1038/s41581-019-0185-9
  • Peer Reviewed
• [Journal Article] The unprecedented era of aging (2019)
  • Author(s): Sato Yuki、Yanagita Motoko
  • Journal Title: Inflammation and Regeneration Volume: 39 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s41232-019-0104-2
  • Peer Reviewed / Open Access
• [Journal Article] Excessive mechanical loading promotes osteoarthritis through the gremlin-1?NF-κB pathway (2019)
  • Author(s): Chang Song Ho、Mori Daisuke、Kobayashi Hiroshi、Mori Yoshifumi、Nakamoto Hideki、Okada Keita、Taniguchi Yuki、Sugita Shurei、Yano Fumiko、Chung Ung-il、Kim-Kaneyama Joo-ri、Yanagita Motoko、Economides Aris、Canalis Ernesto、Chen Di、Tanaka Sakae、Saito Taku
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 1442-1442
  • DOI: 10.1038/s41467-019-09491-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low-dose atrial natriuretic peptide for prevention or treatment of acute kidney injury: a systematic review and?meta-analysis (2019)
  • Author(s): Yamada Hiroyuki、Doi Kent、Tsukamoto Tatsuo、Kiyomoto Hideyasu、Yamashita Kazuto、Yanagita Motoko、Terada Yoshio、Mori Kiyoshi
  • Journal Title: Critical Care Volume: 23 Issue: 1 Pages: 41-41
  • DOI: 10.1186/s13054-019-2330-z
  • Peer Reviewed
• [Journal Article] Myofibroblasts acquire retinoic acid?producing ability during fibroblast-to-myofibroblast transition?following kidney injury (2019)
  • Author(s): Nakamura Jin、Sato Yuki、Kitai Yuichiro、Wajima Shuichi、Yamamoto Shinya、Oguchi Akiko、Yamada Ryo、Kaneko Keiichi、Kondo Makiko、Uchino Eiichiro、Tsuchida Junichi、Hirano Keita、Sharma Kumar、Kohno Kenji、Yanagita Motoko
  • Journal Title: Kidney International Volume: 95 Issue: 3 Pages: 526-539
  • DOI: 10.1016/j.kint.2018.10.017
  • NAID: 120006550402
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Everolimus delayed and suppressed cytomegalovirus DNA synthesis, spread of the infection, and alleviated cytomegalovirus infection (2019)
  • Author(s): Tan Long、Sato Noriaki、Shiraki Atsuko、Yanagita Motoko、Yoshida Yoshihiro、Takemura Yoshinori、Shiraki Kimiyasu
  • Journal Title: Antiviral Research Volume: 162 Pages: 30-38
  • DOI: 10.1016/j.antiviral.2018.12.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Immune cells and inflammation in AKI to CKD progression (2018)
  • Author(s): Sato Yuki、Yanagita Motoko
  • Journal Title: American Journal of Physiology-Renal Physiology Volume: 315 Issue: 6 Pages: F1501-F1512
  • DOI: 10.1152/ajprenal.00195.2018
  • Peer Reviewed
• [Journal Article] CTGF in kidney fibrosis and glomerulonephritis (2018)
  • Author(s): Toda Naohiro、Mukoyama Masashi、Yanagita Motoko、Yokoi Hideki
  • Journal Title: Inflammation and Regeneration Volume: 38 Issue: 1 Pages: 14-14
  • DOI: 10.1186/s41232-018-0070-0
  • Peer Reviewed
• [Journal Article] Loss of periostin ameliorates adipose tissue inflammation and fibrosis in vivo (2018)
  • Author(s): Nakazeki Fumiko、Nishiga Masataka、Horie Takahiro、Nishi Hitoo、Nakashima Yasuhiro、Baba Osamu、Kuwabara Yasuhide、Nishino Tomohiro、Nakao Tetsushi、Ide Yuya、Koyama Satoshi、Kimura Masahiro、Tsuji Shuhei、Sowa Naoya、Yoshida Shigeo、Conway Simon J.、Yanagita Motoko、Kimura Takeshi、Ono Koh
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 8553-8553
  • DOI: 10.1038/s41598-018-27009-9
  • NAID: 120006510274
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Guanylyl cyclase A in both renal proximal tubular and vascular endothelial cells protects the kidney against acute injury in rodent experimental endotoxemia models. (2018)
  • Author(s): Kidney against Acute Injury in Rodent Experimental Endotoxemia Models. Kitamura H, Nakano D, Sawanobori Y, Asaga T, Yokoi H, Yanagita M, Mukoyama M, Tokudome T, Kangawa K, Shirakami G, Nishiyama A.
  • Journal Title: Anesthesiology Volume: 印刷中 Issue: 2 Pages: 296-310
  • DOI: 10.1097/aln.0000000000002214
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis (2018)
  • Author(s): Asao Rin、Seki Takuto、Takagi Miyuki、Yamada Hiroyuki、Kodama Fumiko、Hosoe-Nagai Yoshiko、Tanaka Eriko、Trejo Juan Alejandro Oliva、Yamamoto-Nonaka Kanae、Sasaki Yu、Hidaka Teruo、Ueno Takashi、Yanagita Motoko、Suzuki Yusuke、Tomino Yasuhiko、Asanuma Katsuhiko
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5061-5061
  • DOI: 10.1038/s41598-018-23278-6
  • NAID: 120006517798
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease. (2018)
  • Author(s): Iguchi T, Takaori K, Mii A, Sato Y, Suzuki Y, Yoshifuji H, Seno H, Ogawa O, Omori K, Bessho K, Kondo S, Yoshizaki T, Nakashima H, Saito T, Mimori T, Haga H, Kawano M, Yanagita M.
  • Journal Title: Mod Pathol. Volume: - Issue: 6 Pages: 890-899
  • DOI: 10.1038/s41379-018-0036-4
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mechanisms of AKI to CKD Transition (2019)
  • Author(s): Motoko Yanagita
  • Organizer: Asia Pacific AKI to/onCKD Summit 2019
  • Int'l Joint Research / Invited
• [Presentation] Essential Roles of Testosterone in Male Kidney Maturation and Repair After Injury (2019)
  • Author(s): Yuki Sato, Eiichiro Uchino, Akiko Oguchi, Yuichiro Kitai, Shushi Nagamori, Yoshikatsu Kanai, Yasuhiro Murakawa , Motoko Yanagita
  • Organizer: Kidney week 2019
  • Int'l Joint Research
• [Presentation] Tertiary Lymphoid Tissues in Protocol Biopsies Predict Progressive Graft Dysfunction in Kidney Transplant Recipients (2019)
  • Author(s): Yu ho Lee, Yuki Sato, Mitsuru Saito, Shingo Fukuma, Nobuhiro Fujiyama, Shigeru Satoh, Sangho Lee, Tomonori Habuchi, Motoko Yanagita
  • Organizer: Kidney week 2019
  • Int'l Joint Research
• [Presentation] Genome-Wide Identification of Active Enhancers in Renal Aging (2019)
  • Author(s): Akiko Oguchi, Motoko Yanagita, Yasuhiro Murakawa
  • Organizer: Kidney week 2019
  • Int'l Joint Research
• [Presentation] A Novel Kidney Slice Culture System Visualizing Intrarenal ATP and Segment-Dependent Energy Metabolism (2019)
  • Author(s): Shigenori Yamamoto, Shinya Yamamoto, Masamichi Yamamoto, Motoko Yanagita
  • Organizer: Kidney week 2019
  • Int'l Joint Research
• [Presentation] Spatiotemporal ATP Dynamics In Podocytes During Ischemic Reperfusion Injury Predicts Later Foot Process Effacement (2019)
  • Author(s): Masahiro Takahashi, Shigenori Yamamoto, Masamichi Yamamoto, Motoko Yanagita
  • Organizer: Kidney week 2019
  • Int'l Joint Research
• [Presentation] Transiently Dedifferentiated eR1-Active Proximal Tubule Cells Clonally Expand and Repair Proximal Tubules in Severe Injury (2019)
  • Author(s): Yuichiro Kitai, Motoko Yanagita
  • Organizer: Kidney week 2019
  • Int'l Joint Research
• [Presentation] 腎臓の老化と炎症 (2019)
  • Author(s): 佐藤有紀、柳田素子
  • Organizer: 第49回日本腎臓学会西部学術大会
• [Presentation] Inflammation and aging (2019)
  • Author(s): Motoko Yanagita
  • Organizer: FASEB meeting
  • Int'l Joint Research / Invited
• [Presentation] EPO産生細胞に関する最新の知見 (2019)
  • Author(s): 柳田素子
  • Organizer: 第64回日本透析医学会学術集会・総会
  • Invited
• [Presentation] 腎障害における線維化の正の側面：myofibroblastのレチノイン酸合成能獲得 (2019)
  • Author(s): 中村仁、北井悠一朗、佐藤有紀、柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] 急性腎障害から慢性腎臓病移行へのメカニズム (2019)
  • Author(s): 柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
  • Invited
• [Presentation] 腎スライス培養を用いたATPイメージング系の樹立と各ネフロンセグメントにおけるATP産生機構の検討 (2019)
  • Author(s): 山本恵則、高橋昌宏、山本伸也、今村博臣、山本正道、柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] 重度障害では,RUNX1エンハンサー eR1が活性化した近位尿細管上皮細胞が強く増殖し,近位尿細管を修復する (2019)
  • Author(s): 北井悠一朗、大里元美、柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] 腎の機能成熟と障害抵抗性のパラドックス (2019)
  • Author(s): 北井悠一朗、佐藤有紀、小口綾貴子、村川泰裕、柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] Inflammaging in the kidney (2019)
  • Author(s): 柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
  • Invited
• [Presentation] Onconephrology：腫瘍学と腎臓病学をつなぐ新領域 (2019)
  • Author(s): 柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
  • Invited
• [Presentation] 男性ホルモンによる腎成熟制御機構の多層的オミックス解析 (2019)
  • Author(s): 佐藤有紀、北井悠一朗、内野詠一郎、小口綾貴子、永森收志、金井好克、曽我朋義、村川泰裕、柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] 広域電子顕微鏡から切り拓く腎臓の再解析 (2019)
  • Author(s): 小口綾貴子、前田光代、須賀三雄、田村勝、片岡洋祐、柳田素子
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] 生体腎におけるATPイメージング法の確立およびATP動態と腎予後の関連性の解析 (2019)
  • Author(s): 山本伸也、山本恵則、高橋昌宏、山本正道、柳田素子
  • Organizer: 第116回日本内科学会総会・講演会
• [Presentation] 新規遺伝子組み換えマウスを用いたエリスロポエチン（Epo）産生細胞の系譜追とその特徴的な拳動の検討 (2019)
  • Author(s): 金子惠一、浅田三咲子、柳田素子
  • Organizer: 第116回日本内科学会総会・講演会
• [Presentation] Onco-nephrology (2019)
  • Author(s): 柳田素子
  • Organizer: 第116回日本内科学会総会・講演会
  • Invited
• [Presentation] Pathophysiology, diagnosis and prediction (2019)
  • Author(s): Motoko Yanagita
  • Organizer: ISN WCN 2019
  • Int'l Joint Research / Invited