Analysis of a role of ADAMTS13 regarding thrombus formation in kidney

• Project/Area Number: 17K16073
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIDA YOKO 東京大学, 医学部附属病院, 特任研究員 (90649443)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ADAMTS13 / VWF / 腎炎 / 血小板 / 血栓性微小血管症

Outline of Final Research Achievements

ADAMTS13 is a specific cleaving protease of von Willebrand factor (VWF), which is a blood glycoprotein involved in hemostasis and thrombosis. In this study, we aim to clarify the effect of ADAMTS13 deficiency on kidney failure (with or without thrombotic microangiopathy) and the role of ADAMTS13 expressed in the kidney. Consequently, we revealed that some kind of challenge related to renal damage led to decreased survival and TTP-like symptoms in ADAMTS13 deficient mice. The results of this study may provide insights into the molecular mechanisms of ADAMTS13-mediated antithrombotic effect in the kidney.

Academic Significance and Societal Importance of the Research Achievements

ADAMTS13-VWFと腎臓との関係性は未だ不明な点が多く、本研究の成果はADAMTS13を介した腎臓における血栓制御機構に新たな知見をもたらすことが期待される。また近年、先天性の血栓性血小板減少性紫斑病患者への新規治療薬として遺伝子組み換え型ADAMTS13の有効性が期待されているが、本研究の成果は将来的にこのような薬剤の腎臓における治療効果を提示し得る可能性を秘めており、社会的にも重要性が高いと考えられる。

Research Products

• [Journal Article] Profiles of Coagulation and Fibrinolysis Activation-Associated Molecular Markers of Atypical Hemolytic Uremic Syndrome in the Acute Phase (2020)
  • Author(s): Sakurai S, Kato H, Yoshida Y, Sugawara Y, Fujisawa M, Yasumoto A, Matsumoto M, Fujimura Y, Yatomi Y, Nangaku M
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 27 Issue: 4 Pages: 353-362
  • DOI: 10.5551/jat.49494
  • NAID: 130007824992
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2020-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenesis of Atypical Hemolytic Uremic Syndrome (2019)
  • Author(s): Yoshida Yoko、Kato Hideki、Ikeda Yoichiro、Nangaku Masaomi
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 26 Issue: 2 Pages: 99-110
  • DOI: 10.5551/jat.RV17026
  • NAID: 130007590038
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2019-02-01
  • Peer Reviewed / Open Access
• [Journal Article] Atypical Hemolytic Uremic Syndrome With the p.Ile1157Thr C3 Mutation Successfully Treated With Plasma Exchange and Eculizumab: A Case Report (2019)
  • Author(s): Saito D, Watanabe E, Ashida A, Kato H, Yoshida Y, Nangaku M, Ohtsuka Y, Miyata T, Hattori N, Oda S.
  • Journal Title: Crit Care Explor. Volume: 1 Issue: 4 Pages: e0008-e0008
  • DOI: 10.1097/cce.0000000000000008
  • Peer Reviewed / Open Access
• [Journal Article] Novel CFHR2-CFHR1 Hybrid in C3 Glomerulopathy Identified by Genomic Structural Variation Analysis (2019)
  • Author(s): Sugawara Y, Kato H, Yoshida Y, Fujisawa M, Kokame K, Miyata T, Akioka Y, Miura K, Hattori M, Nangaku M.
  • Journal Title: Kidney Int Rep. Volume: 4 Issue: 12 Pages: 1759-1762
  • DOI: 10.1016/j.ekir.2019.09.008
  • Peer Reviewed / Open Access
• [Journal Article] Clinical manifestation of patients with atypical hemolytic uremic syndrome with the C3 p.I1157T variation in the Kinki region of Japan. (2018)
  • Author(s): Matsumoto T, Toyoda H, Amano K, Hirayama M, Ishikawa E, Fujimoto M, Ito M, Ohishi K, Katayama N, Yoshida Y, Matsumoto M, Kawamura N, Ikejiri M, Kawakami K, Miyata T, Wada H
  • Journal Title: Clin Appl Thromb Hemost Volume: 24 Issue: 8 Pages: 1301-1307
  • DOI: 10.1177/1076029618771750
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome (2018)
  • Author(s): Fujisawa Madoka、Kato Hideki、Yoshida Yoko、Usui Tomoko、Takata Munenori、Fujimoto Mika、Wada Hideo、Uchida Yumiko、Kokame Koichi、Matsumoto Masanori、Fujimura Yoshihiro、Miyata Toshiyuki、Nangaku Masaomi
  • Journal Title: Clinical and Experimental Nephrology Volume: 印刷中 Issue: 5 Pages: 1088-1099
  • DOI: 10.1007/s10157-018-1549-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alternative pathway activation due to low level of complement factor H in primary antiphospholipid syndrome (2018)
  • Author(s): Nakamura H, Oku K, Ogata Y, Ohmura K, Yoshida Y, Kitano E, Fujieda Y, Kato M, Bohgaki T, Amengual O, Yasuda S, Fujimura Y, Seya T, Atsumi T
  • Journal Title: Thrombosis Research Volume: 164 Pages: 63-68
  • DOI: 10.1016/j.thromres.2018.02.142
  • Peer Reviewed
• [Journal Article] Functional splicing analysis in an infantile case of atypical hemolytic uremic syndrome caused by digenic mutations in C3 and MCP genes (2018)
  • Author(s): Yamamura Tomohiko、Nozu Kandai、Ueda Hiroaki、Fujimaru Rika、Hisatomi Ryutaro、Yoshida Yoko、Kato Hideki、Nangaku Masaomi、Miyata Toshiyuki、Sawai Toshihiro、Minamikawa Shogo、Kaito Hiroshi、Matsuo Masafumi、Iijima Kazumoto
  • Journal Title: Journal of Human Genetics Volume: Epub ahead of print Issue: 6 Pages: 755-759
  • DOI: 10.1038/s10038-018-0436-9
  • Peer Reviewed
• [Journal Article] Severe reduction of free-form ADAMTS13, unbound to von Willebrand factor, in plasma of patients with HELLP syndrome (2017)
  • Author(s): Yoshida Yoko、Matsumoto Masanori、Yagi Hideo、Isonishi Ayami、Sakai Kazuya、Hayakawa Masaki、Hori Yuji、Sado Toshiyuki、Kobayashi Hiroshi、Fujimura Yoshihiro
  • Journal Title: Blood Advances Volume: 1 Issue: 20 Pages: 1628-1631
  • DOI: 10.1182/bloodadvances.2017006767
  • NAID: 130007431929
  • Peer Reviewed / Open Access
• [Journal Article] Atypical Hemolytic Uremic Syndrome (2017)
  • Author(s): Yoshida Y, Kato H and Nangaku M.
  • Journal Title: Renal Replacement Therapy. Volume: 3 Issue: 1 Pages: 1-10
  • DOI: 10.1186/s41100-016-0088-1
  • NAID: 40021361310
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 免疫学的腎炎モデルにおける血栓制御機構の関わり (2021)
  • Author(s): 吉田瑶子、西裕志、稲城玲子、南学正臣
  • Organizer: 第64回 日本腎臓学会学術総会
• [Presentation] 抗Factor H自己抗体による非典型溶血性尿毒症症候群 (2019)
  • Author(s): 吉田瑶子
  • Organizer: 第26回自己抗体と自己免疫シンポジウム
  • Invited
• [Presentation] Severe reduction of free-form ADAMTS13, unbound to von Willebrand factor, in plasma of patients with HELLP syndrome (2018)
  • Author(s): Yoshida Yoko
  • Organizer: 第40回 日本血栓止血学会
  • Invited