Pathophysiological function of CLEC-2 for megaakryocyte and erythrocyte development

• Project/Area Number: 26860723
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Nagoya University (2015-2016); University of Yamanashi (2014)
• Principal Investigator: Tamura Shogo 名古屋大学, 医学系研究科(保健), 助教 (60722626)
• Research Collaborator: Inoue Katsue (Suzuki Katsue) ; Ozaki Yukio ; Tsukiji Nagaharu ; Shirai Toshiaki
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 巨核球 / CLEC-2 / 骨髄微小環境 / 巨核球造血

Outline of Final Research Achievements

C-type lectin-like receptor 2 (CLEC-2) is a platelet activating receptor which binds to podoplanin (PDPN). In this study, we investigated a physiological function of CLEC-2 and/or PDPN for meagkaryo/thrombopoiesis. The interaction of CLEC-2 with PDPN directly accelerated expansion of megakaryocyte progenitors. We also newly identified PDPN expressing bone marrow stromal cells adjacent to arterioles in the bone marrow, and termed as BM FRC-like cells. Now, we propose that BM FRC-like cells provide a novel CLEC-2/PDPN dependent megakaryopoietic microenvironment in the vicinity of arterioles in the bone marrow.

Research Products

• [Journal Article] 血小板・巨核球造血微小環境を構成する骨髄間質細胞 (2017)
  • Author(s): 田村彰吾、尾崎由基男、小嶋哲人、井上克枝
  • Journal Title: 日本血栓止血学会誌 Volume: 28 Pages: 59-63
  • NAID: 130005338029
• [Journal Article] The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities. (2017)
  • Author(s): Furuya, Fumihiko Ishii, Toshihisa Tamura, Shogo Takahashi, Kazuya Kobayashi, Hidetoshi Ichijo, Masashi Takizawa, Soichi Kaneshige, Masahiro Suzuki-Inoue, Katsue Kitamura, Kenichiro
  • Journal Title: Scientific reports Volume: 7 Issue: 1 Pages: 43960-43960
  • DOI: 10.1038/srep43960
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Progestin isoforms provide different levels of protein S expression in HepG2 cells. (2016)
  • Author(s): Kozuka, Toshihiro Tamura, Shogo Kawamura, Nami Nakata, Yukiko Hasebe, Ryo Makiyama, Ayumi Takagi, Yuki Murata, Moe Mizutani, Naoki Takagi, Akira Kojima, Tetsuhito
  • Journal Title: Thrombosis research Volume: 145 Pages: 40-5
  • DOI: 10.1016/j.thromres.2016.07.007
  • NAID: 120005895232
  • Peer Reviewed
• [Journal Article] Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance (2016)
  • Author(s): Takagi Y, Murata M, Kozuka T, Nakata Y, Hasebe R, Tamura S, Takagi A, Matsushita T, Saito H, Kojima T.
  • Journal Title: THROMBOSIS AND HAEMOSTASIS Volume: 116 Issue: 12 Pages: 1022-31
  • DOI: 10.1160/th16-03-0223
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] New horizon in platelet function: with special reference to a recently-found molecule, CLEC-2. (2016)
  • Author(s): Ozaki, Yukio Tamura, Shogo Suzuki-Inoue, Katsue
  • Journal Title: Thrombosis journal Volume: 14 Issue: S1 Pages: 27-27
  • DOI: 10.1186/s12959-016-0099-8
  • Peer Reviewed
• [Journal Article] CLEC-2 promotes hematogenous tumor metastasis and prothrombotic state in tumor-bearing mice. (2016)
  • Author(s): Shirai, Toshiaki Inoue, Osamu Tamura, Shogo Tsukiji, Nagaharu Sasaki, Tomoyuki Endo, Hiroshi Satoh, Kaneo Osada, Makoto Sato-Uchida, Hitomi Fujii, Hideki Ozaki, Yukio Suzuki-Inoue, Katsue
  • Journal Title: Journal of thrombosis and haemostasis Volume: 38 Issue: 3 Pages: 42-49
  • DOI: 10.1111/jth.13604
  • Peer Reviewed
• [Journal Article] Podoplanin-positive periarteriolar stromal cells promote megakaryocyte growth and proplatelet formation in mice by CLEC-2 (2016)
  • Author(s): TAMURA Shogo, SUZUKI-INOUE Katsue, TSUKIJI Nagaharu, SHIRAI Toshiaki, SASAKI Tomoyuki, OSADA Makoto, SATOH Kaneo, OZAKI Yukio
  • Journal Title: Blood Volume: 127 Issue: 13 Pages: 1701-1710
  • DOI: 10.1182/blood-2015-08-663708
  • NAID: 130007432250
  • Peer Reviewed
• [Journal Article] CD36の発現多様性 欠損症および健常者の発現分子数のバラつき (2015)
  • Author(s): 田村彰吾、増田裕弥、松野一彦、尾崎由基男
  • Journal Title: 検査と技術 Volume: 43 Pages: 186-188
• [Journal Article] Diverse CD36 expression among Japanese population: defective CD36 mutations cause platelet and monocyte CD36 reductions in not only deficient but also normal phenotype subjects (2015)
  • Author(s): Masuda Y, Tamura S, Matsuno K, Nagasawa A, Hayasaka K, Shimizu C, Moriyama T
  • Journal Title: Thrombosis Research Volume: 135 Issue: 5 Pages: 951-957
  • DOI: 10.1016/j.thromres.2015.03.002
  • Peer Reviewed
• [Journal Article] Measurement of soluble C-type lectin-like receptor 2 in human plasma (2015)
  • Author(s): Kazama F, Nakamura J, Osada M, Inoue O, Oosawa M, Tamura S, Tsukiji N, Aida K, Kawaguchi A, Takizawa S, Kaneshige A, Tanaka S, Suzuki-Inoue K, & Ozaki Y
  • Journal Title: Platelets Volume: 26 Issue: 8 Pages: 711-719
  • DOI: 10.3109/09537104.2015.1021319
  • Peer Reviewed
• [Journal Article] Laboratory and clinical features of abnormal macroenzymes found in human sera (2014)
  • Author(s): Moriyama T, Tamura S, Nakano K, Otsuka K, Shigemura M, Honma N
  • Journal Title: BBA Proteins and Proteomics Volume: 1854 Issue: 6 Pages: 658-667
  • DOI: 10.1016/j.bbapap.2014.10.015
  • Peer Reviewed
• [Presentation] Novel periarteriolar stromal cells promote megakaryo/thrombopoiesis via CLEC-2/podoplanin binding (2016)
  • Author(s): Shogo Tamura, Katsue Suzuki-Inoue, Yukio Ozaki, Nagaharu Tsukiji, Toshiaki Shirai, Tomoyuki Sasaki, Makoto Osada, Kaneo Satoh, Akira Takagi, Tetsuhito Kojima
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-13
• [Presentation] Diverse F9 abnormalities including a large SVA retrotransposon insertion that cause hemophilia B (2016)
  • Author(s): 坂根 寛人,中村 友紀,藤岡 亮也,橋本 恵梨華,槇山 愛弓,河村 奈美,鈴木 幸子,高木 夕希,田村 彰吾,高木 明, 小川実加,兼松毅,岸本磨由子,鈴木 伸明,松下 正, 小嶋 哲人
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-13
• [Presentation] A novel megakaryopoietic microenvironment in the bone marrow: Podoplanin-positive peri-arteriolar stromal cells regulate megakaryocyte proliferation and proplatelet formation via CLEC-2 binding (2016)
  • Author(s): Shogo Tamura, Katsue Suzuki-Inoue, Nagaharu Tsukiji, Toshiaki Shirai, Tomoyuki Sasaki, Makoto Osada, Kaneo Satoh, Yukio Ozaki
  • Organizer: 第38回日本血栓止血学会学術集会
  • Place of Presentation: 奈良春日野国際フォーラム
  • Year and Date: 2016-06-16
  • Invited
• [Presentation] A novel function of CLEC-2 in megakaryopoiesis: CLEC-2/PDPN microenvironment facilitates expansion and maturation of megakaryocytes (2015)
  • Author(s): Tamura S, Suzuki-Inoue K, Tsukiji N, Shirai T, Sasaki T, Osada M, Satoh K, Ozaki Y
  • Organizer: XXV congress of The international society on Thrombosis and Heamostasis (ISTH2015)
  • Place of Presentation: Toronto
  • Year and Date: 2015-07-25
  • Int'l Joint Research
• [Presentation] The defective CD36 gene mutations cause a molecular expression diversity on platelets and monocytes even in non-deficient phenotype population (2015)
  • Author(s): Masuda Y, Tamura S, Matsuno K, Hayasaka K, Shimizu C, Moriyama T
  • Organizer: XXV congress of The international society on Thrombosis and Heamostasis (ISTH2015)
  • Place of Presentation: Toronto
  • Year and Date: 2015-07-24
  • Int'l Joint Research
• [Presentation] Construction of expression system for biologically functional recombinant rhodocytin (2015)
  • Author(s): Sasaki T, Tamura S, Shirai T, Tsukiji N, Satoh K, Suzuki-Inoue K, Ozaki Y
  • Organizer: XXV congress of The international society on Thrombosis and Heamostasis (ISTH2015)
  • Place of Presentation: Toronto
  • Year and Date: 2015-07-23
  • Int'l Joint Research
• [Presentation] Unexpected role of platelets in lung development depending on a platelet activation receptor, CLEC-2 (2015)
  • Author(s): Tsukiji N, Inoue O, Tamura S, Shirai T, Sasaki T, Satoh K, Suzuki-Inoue K, Ozaki Y
  • Organizer: XXV congress of The international society on Thrombosis and Heamostasis (ISTH2015)
  • Place of Presentation: Toronto
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] CLEC-2/PDPN axisを介した巨核球造血微小環境 (2015)
  • Author(s): 田村彰吾、井上克枝、築地長治、白井俊光、佐々木知幸、佐藤金夫、尾崎由基男
  • Organizer: 第16回日本検査血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-07-11
• [Presentation] CLEC-2/PDPN axisによる骨髄内微小環境の可能性：CLEC-2は巨核球造血を促進させる (2015)
  • Author(s): 田村彰吾、井上克枝、白井俊光、築地長治、佐々木知幸、佐藤金夫、尾崎由基男
  • Organizer: 第37回日本血栓止血学会学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2015-05-23
• [Presentation] 可溶性CLEC-2は血小板活性化に伴って生成される：可溶性GPVIとの比較検討 (2015)
  • Author(s): 井上修、長田誠、中村純也、風間文智、横道洋司、土肥智貴、金子誠、蔵野信、大澤満、田村彰吾、佐藤金夫、高野勝弘、宮内克己、代田浩之、矢富裕、井上克枝、尾崎由基男
  • Organizer: 第37回日本血栓止血学会学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2015-05-23
• [Presentation] 血小板は胚発生に必須である：血小板CLEC-2の機能解析 (2015)
  • Author(s): 築地長治、井上修、田村彰吾、白井俊光、佐々木知幸、佐藤金夫、井上克枝、尾崎由基男
  • Organizer: 第37回日本血栓止血学会学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2015-05-23
• [Presentation] 血小板活性化受容体CLEC-2結合蛇毒ロドサイチンの機能を保持したリコンビナント体発現系の構築 (2015)
  • Author(s): 佐々木知幸、田村彰吾、白井俊光、築地長治、佐藤金夫、井上克枝、尾崎由基男
  • Organizer: 第37回日本血栓止血学会学術集会
  • Place of Presentation: 山梨
  • Year and Date: 2015-05-23
• [Presentation] A novel function of CLEC-2 for megakaryopoiesis: CLEC-2/PDPN niche promotes megakaryocyte expansion (2015)
  • Author(s): Shogo Tamura, Katsue Suzuki-Inoue, Toshiaki Shirai, Nagaharu Tsukiji, Kaneo Satoh, Yukio Ozaki
  • Organizer: Joint International Symposium on TGF-b Family and Cancer Signal Network in Tumor Microenvironment
  • Place of Presentation: International congress center EPOCHAL TSUKUBA (Tsukuba, Ibaraki)
  • Year and Date: 2015-01-12 – 2015-01-13
• [Presentation] 血小板・単球におけるCD36 分子発現の多様性と遺伝子変異との関連 (2014)
  • Author(s): 増田 裕弥，田村 彰吾，松野 一彦，早坂 光司，渋谷 斉，清水 力，森山 隆則
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡国際会議場 （福岡県福岡市）
  • Year and Date: 2014-11-23
• [Presentation] 巨核球造血におけるCLEC-2 の病態生理学的作用の解析 (2014)
  • Author(s): 田村 彰吾，井上 克枝，白井 俊光，築地 長治，佐藤 金夫，尾崎由基男
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡国際会議場 （福岡県福岡市）
  • Year and Date: 2014-11-23
• [Presentation] Vacuolating cytotoxin A (VacA) of Helicobactor Pylori binds to Multimerin1 (2014)
  • Author(s): Kaneo Satoh, Toshiya Hirayama, Masato Ohta, Shogo Tamura, Yuko Ozaki
  • Organizer: The 3rd World Congress on Controversies in Hematology
  • Place of Presentation: The Marmara Taksim Hotel (Instanbul, Turkey)
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 血小板におけるCD36発現分子数の低下と活性化による変化 (2014)
  • Author(s): 増田裕弥、田村彰吾、長澤あゆみ、松野一彦、進藤由衣香、早坂光司、渋谷 斉、清水 力、森山隆則
  • Organizer: 第15回日本検査血液学会学術集会
  • Place of Presentation: 仙台国際センター （宮城県仙台市）
  • Year and Date: 2014-07-20
• [Presentation] 血小板におけるCD36分子発現量の多様性と一塩基多型(C268T)の関連 (2014)
  • Author(s): 増田裕弥、田村彰吾、長澤あゆみ、松野一彦、進藤由衣香、早坂光司、渋谷 斉、清水 力、尾崎由基男、森山隆則
  • Organizer: 第36回日本血栓止血学会学術集会
  • Place of Presentation: 大阪国際交流センター （大阪府大阪市）
  • Year and Date: 2014-05-30
• [Presentation] Unexpected role of blood platelets in lung development depending on a novel platelet activation receptor, CLEC-2 (血小板が正常な肺発生を可能にする - 新規血小板活性化受容体CLEC-2の機能解析 - ) (2014)
  • Author(s): Nagaharu Tsukiji, Osamu Inoue, Shogo Tamura, Toshiaki Shirai, Katsue Suzuki-Inoue, Yukio Ozaki
  • Organizer: 第47回日本発生生物学会
  • Place of Presentation: WINC AICHI (愛知県名古屋市)
  • Year and Date: 2014-05-27
• [Remarks] 名古屋大学大学院医学系研究科 医療技術学専攻 病態解析学講座 分子病態解析学部門 血液・遺伝子研究室
  • URL: http://square.umin.ac.jp/bloodlab/Hematol_%26_Gene_Res_Lab/Welcome.html
• [Remarks] 山梨大学医学部臨床検査医学講座
  • URL: http://www.med.yamanashi.ac.jp/clinical/clin0lab/
• [Remarks] 山梨大学 臨床検査医学講座 ホームページ
  • URL: http://www.med.yamanashi.ac.jp/clinical/clin0lab/