Progranulin, a Novel HDL-Binding Protein, Suppresses Systemic Inflammation, Glucose Abnormality and Atherosclerosis

• Project/Area Number: 24390233
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka University
• Principal Investigator: YAMASHITA Shizuya 大阪大学, 医学(系)研究科(研究院), 寄附講座教授 (60243242)
• Co-Investigator(Kenkyū-buntansha): MASUDA Daisaku 大阪大学, 大学院医学系研究科, 特任助教 (20568753)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: プログラニュリン / マクロファージ / 炎症 / HDL / 動脈硬化 / 認知症 / 急性冠症候群

Outline of Final Research Achievements

While progranulin (PGRN) has been reported to be involved with cell proliferation, wound healing and inflammation, there were no direct information on the association of progranulin with atherosclerosis. Therefore, we crossed apoE-knockout(KO) mce with PGRN-KO mice to generate double-KO (DKO) mice. DKO mice exhibit more severe atherosclerosis compared with apoE-KO mice. Considering PGRN is associated with various inflammatory diseases, PGRN can be a novel therapeutic target for atherosclerotic and inflammatory diseases.

Research Products

• [Journal Article] Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice. (2013)
  • Author(s): Kawase R, Ohama T, Matsuyama A, Matsuwaki T, Okada T, Yamashita T, Yuasa-Kawase M, Nakaoka H, Nakatani K, Inagaki M, Tsubakio-Yamamoto K, Masuda D, Nakagawa-Toyama Y, Nishida M, Ohmoto Y, Nishihara M, Komuro I, Yamashita S.
  • Journal Title: Cardiovascular Research Volume: 100 Issue: 1 Pages: 125-133
  • DOI: 10.1093/cvr/cvt178
  • Peer Reviewed
• [Presentation] A Role of Progranulin in Acute Coronary Syndrome (2014)
  • Author(s): R Kawase, T Ohama, M Morita, Y Kurozumi, N Ito, T Okada, D Masuda, M Koseki, M Nishida, H Sawano, Y Doi, Y Sakata, S Yamashita
  • Organizer: AHA2014
  • Place of Presentation: San Francisco,America
  • Year and Date: 2014-11-18
• [Presentation] Progranulin plays a crucial role in the development of atherosclerosis (2014)
  • Author(s): R Kawase, T Ohama, A Matsuyama, Y Zhu, T Okada, K Nakatani, D Masuda, M Koseki, M Nishida, Y Sakata, S Yamashita
  • Organizer: MSDA2014
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-09-13
• [Presentation] 抗炎症性蛋白progranulin（PGRN）の急性冠症候群発症における役割 (2014)
  • Author(s): 川瀬 良太、大濱 透、森田 雅也、黒住 祐磨、夏川 知輝、伊藤 賀敏、増田 大作、小関 正博、西田 誠、澤野 宏隆、土井 泰治、坂田 泰史、山下 静也
  • Organizer: 第46回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2014-07-11
• [Presentation] Progranulin Plays a Crucial Role in the development of Atherosclerosis (2014)
  • Author(s): Ryota Kawase, Tohru Ohama, Akifumi Matsuyama, Yinghong Zhu,Takeshi Okada, Hajime Nakaoka, Miyako Yuasa-Kawase, Kazuhiro Nakatani, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Yasushi Sakata and Shizuya Yamashita
  • Organizer: 第７８回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Deletion of Progranulin Exacerbates Atherosclerosis by Changing HDL-associated Antiatherogenic Proteins and Altering Cholesterol Homeostasis (2013)
  • Author(s): 大濱透
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-03-15
• [Presentation] Deficiency of Progranulin Aggravates Atherosclerosis Possibly Due to Enhanced Inflammation (2013)
  • Author(s): 川瀬良太
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-03-15
• [Presentation] Deficiency of Progranulin Aggravates Atherosclerosis Partly Due to Enhanced Inｆｌammation and Impairment of Endothelial Function (2013)
  • Author(s): Ryota Kawase, Tohru Ohama, Akifumi Matsuyama, Takeshi Okada, Hajime Nakaoka, Miyako Kawase, Kazuhiro Nakatani, Kazumi Yamamoto, Daisaku Masuda, Yumiko Toyama, Makoto Nishida, Issei Komuro and Shizuya Yamashita
  • Organizer: 第４５回日本動脈硬化学会総会・学術総会
  • Place of Presentation: 京王プラザホテル（新宿）
• [Presentation] Deletion of Progranulin Exacerbates Atherosclerosis by ChangiHDL-associated Proteins and Altering Cholesterol Homeostasis (2013)
  • Author(s): Tohru Ohama, Ryota Kawase, Akifumi Matsuyama, Takeshi Okada, Hajime Nakaoka, Miyako Yuasa-Kawase, Kazuhiro Nakatani, Daisaku Masuda, Yumiko Nakagawa-Toyama, Makoto Nishida, Issei Komuro and Shizuya Yamashita
  • Organizer: 第４５回日本動脈硬化学会総会・学術総会
  • Place of Presentation: 京王プラザホテル（新宿）
• [Presentation] Deletion of Progranulin Results in Various Metabolic Dysfunctions (2012)
  • Author(s): 大濱透
  • Organizer: 第44回日本動脈硬化学会総会
  • Place of Presentation: ヒルトン福岡シーホーク
  • Year and Date: 2012-07-19
• [Presentation] Deficiency of Progranulin Exacerbates Atherosclerosis in ApoE Knockout mice (2012)
  • Author(s): 川瀬良太
  • Organizer: 第44回日本動脈硬化学会総会
  • Place of Presentation: ヒルトン福岡シーホーク
  • Year and Date: 2012-07-19