Establishment and pathological analysis of novel model mice of systemic chronic inflammation and progeria

• Project/Area Number: 26860263
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: Kawase Ryota 大阪大学, 医学(系)研究科(研究院), 特任研究員 (60727650)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: progranulin / 慢性炎症 / 老化 / PGRN / 炎症 / ﾏｸﾛﾌｧｰｼﾞ / 早期老化

Outline of Final Research Achievements

We revealed that Progranulin (PGRN)・ApoE double KO mice (DKO) died significantly earlier than ApoE KO and often suffered joint swelling and dermatitis, which is considered to be the manifestations of chronic inflammation. Therefore, we hypothesize that DKO might be novel model mice of systemic inflammation and progeria. PGRN have been already reported to bind TNF receptors (TNFRs) and exert anti-inflammatory effects. We find possibility of another pathway other than TNFRs in TNFR KO mice. We also revealed that macrophage-derived PGRN plays important athero-protective roles by using bone marrow transplantation method. And we found that PGRN binding HDL has an anti-oxidative effect. Taken together, PGRN might play essential roles in anti-inflammation and successful aging.

Research Products

• [Journal Article] Methods for studying the function of progranulin in atherosclerosis using both knockout mice models and in vitro studies (2016)
  • Author(s): Ohama T, Kawase R, Yamashita S
  • Journal Title: Methods in Molecular Biology Volume: 未
  • Peer Reviewed
• [Journal Article] Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice (2015)
  • Author(s): Noguchi T, Ebina K, Hirao M, Kawase R, Ohama T, Yamashita S, Morimoto T, Koizumi K, Kitaguchi K, Matsuoka H, Kaneshiro S, Yoshikawa H
  • Journal Title: Biochem Biophys Res Commun. Volume: 465(3) Pages: 638-643
  • Peer Reviewed
• [Journal Article] Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice. (2015)
  • Author(s): Nakatani K, Watabe T, Masuda D, Imaizumi M, Shimosegawa E, Kobayashi T, Sairyo M, Zhu Y, Okada T, Kawase R, Nakaoka H, Naito A, Ohama T, Koseki M, Oka T, Akazawa H, Nishida M, Komuro I, Sakata Y, Hatazawa J, Yamashita S
  • Journal Title: Metabolism Volume: 64(9) Pages: 1165-1174
  • Peer Reviewed
• [Presentation] Macrophage-derived Progranulin Protects from Atherosclerosis (2016)
  • Author(s): Ryota Kawase, Tohru Ohama, Hibiki Matsuda , Masami Sairyo , YingHong Zhu, Takeshi Okada , Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Yasushi Sakata and Shizuya Yamashita
  • Organizer: 第80回 日本循環器学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
• [Presentation] Roles of Progranulin in the stabilization of vulnerable coronary arterial plaques (2015)
  • Author(s): Ryota Kawase, Tohru Ohama, Masaya Morita , Yuma Kurozumi , Noritoshi Ito , Masami Sairyo, Takeshi Okada, Hajime Nakaoka, Kazuhiro Nakatani, Daisaku Masuda, Masahiro Koseki , Makoto Nishida, Hirotaka Sawano , Yasuharu Doi , Yasushi Sakata and Shizuya Yamashita
  • Organizer: 第47回 日本動脈硬化学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2015-07-09
• [Presentation] Roles of an HDL-associated Anti-inflammatory Protein, Progranulin, in Acute Coronary Syndrome (2015)
  • Author(s): Ryota Kawase, Tohru Ohama, Masaya Morita, Yuma Kurozumi, Noritoshi Ito, Masami Sairyo, YingHong Zhu, Takeshi Okada, Hajime Nakaoka, Kazuhiro Nakatani, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Yukihiko Ueda, Hirotaka Sawano, Yasuharu Doi, Yasushi Sakata and Shizuya Yamashita
  • Organizer: 第17回 国際動脈硬化学会
  • Place of Presentation: オランダ
  • Year and Date: 2015-05-23
  • Int'l Joint Research
• [Presentation] Roles of an HDL-associated Anti-inflammatory Protein, Progranulin, in Acute Coronary Syndrome (2015)
  • Author(s): Ryota Kawase, Tohru Ohama, Masaya Morita, Yuma Kurozumi, Noritoshi Ito, Masami Sairyo, YingHong Zhu, Takeshi Okada, Hajime Nakaoka, Kazuhiro Nakatani, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Hirotaka Sawano, Yasuharu Doi, Yasushi Sakata and Shizuya Yamashita
  • Organizer: 第79回 日本循環器学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24