Novel mechanisms of macrophage regulation by u-PA/plasmin system during liver repair

• Project/Area Number: 23790260
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Kinki University
• Principal Investigator: KAWAO Naoyuki 近畿大学, 医学部, 助教 (70388510)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肝修復 / マクロファージ / 組織線溶系 / u-PA

Research Abstract

We investigated novel mechanisms of macrophage regulation by u-PA/plasmin system during liver repair. Our study indicates that u-PA/plasmin system is essential for liver repair through triggering macrophage accumulation at the border region of damaged site. Moreover, u-PA/plasmin system mediates the induction of phenotypic heterogeneity, cell polarity, and phagocytosis of necrotic tissue in the accumulated macrophages by its influence of the surrounding microenvironment at the edge of damaged tissue during liver repair.

Research Products

• [Journal Article] In vivo diagnostic imaging using micro-CT : sequential and comparative evaluation of rodent models for hepatic/brain ischemic and stroke (2012)
  • Author(s): Hayasaka N
  • Journal Title: PLoS One Volume: 7(2) Issue: 2 Pages: e32342-e32342
  • DOI: 10.1371/journal.pone.0032342
  • Peer Reviewed
• [Journal Article] Urokinase-type plasminogen activator and plasminogen mediate activation of macrophage phagocytosis during liver repair in vivo. (2012)
  • Author(s): Kawao N, Nagai N, Tamura Y, Horiuchi Y, Okumoto K, Okada K, Suzuki Y, Umemura K, Yano M, Ueshima S, Kaji H, Matsuo O.
  • Journal Title: Thromb Haemost Volume: 107 Issue: 04 Pages: 749-59
  • DOI: 10.1160/th11-08-0567
  • Peer Reviewed
• [Journal Article] Spatiotemporal differences in vascular permeability after ischaemic brain damage (2011)
  • Author(s): Yano M, Kawao N, Tamura Y, Okada K, Ueshima S, Nagai N, Matsuo O.
  • Journal Title: Neuroreport Volume: 22 Issue: 9 Pages: 424-7
  • DOI: 10.1097/wnr.0b013e3283462dd9
  • Peer Reviewed
• [Journal Article] A synthetic peptide derived from staphylokinase enhances plasminogen activator by tissue-type plasminogen activator. (2011)
  • Author(s): Okada K, Ueshima S, Matsuno H, Nagai N, Kawao N, Tanaka M, Matsuo O.
  • Journal Title: J Thromb Haemost Volume: 9 Issue: 5 Pages: 997-1006
  • DOI: 10.1111/j.1538-7836.2011.04257.x
  • Peer Reviewed
• [Journal Article] Profibrinolytic effect of Enzamin, an extract of metabolic products from Bacillus subtilis AK and Lactobacillus (2011)
  • Author(s): Tamura Y, Okada K, Ueshima S, Matsuo O(他3名)
  • Journal Title: J Thromb Thrombolysis Volume: 32(2) Issue: 2 Pages: 195-200
  • DOI: 10.1007/s11239-011-0552-2
  • Peer Reviewed
• [Journal Article] Urokinase-type plasminogen activator contributes to heterogeneity of macrophages at the border of damaged site during liver repair in mice. (2010)
  • Author(s): Kawao N, Nagai N, Tamura Y, Okada K, Yano M, Suzuki Y, Umemura K, Ueshima S, Matsuo O.
  • Journal Title: Thromb Haemost Volume: 105 Issue: 05 Pages: 892-900
  • DOI: 10.1160/th10-08-0516
  • Peer Reviewed
• [Presentation] Role of the fibrinolytic system in recovery responses after liver injury (2013)
  • Author(s): 河尾直之 他
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形県、山形国際ホテル
• [Presentation] u-PA plays a critical role in the induction of macrophage polarity during liver repair (2012)
  • Author(s): Kawao N, Nagai N, Matsuo O.
  • Organizer: 21st International Congress on Fibrinolysis & Proteolysis
  • Place of Presentation: Brighton UK
• [Presentation] 肝修復過程におけるu-PAによるマクロファージの機能制御 (2012)
  • Author(s): 河尾直之,永井信夫,田村行識,堀内喜高,奥本勝美,岡田清孝,矢野昌人,鈴木康裕,梅村和夫,梶 博史,松尾 理
  • Organizer: 第34回日本血栓止血学会
  • Place of Presentation: 東京都新宿区
• [Presentation] Roles of urokinase-type plasminogen activator and plasminogen in both accumulation of macrophages and induction of their phenotype heterogeneity during liver repair (2012)
  • Author(s): 河尾直之,永井信夫,田村行識,奥本勝美,岡田清孝,矢野昌人,鈴木康裕,梅村和夫,梶 博史,松尾 理
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野県松本市
• [Presentation] Macrophages are regulated by urokinase-type plasminogen activator during liver repair (2012)
  • Author(s): 河尾直之,永井信夫,田村行識,奥本勝美,鈴木康裕,梅村和夫,岡田清孝,矢野昌人,梶 博史,松尾 理
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都府京都市
• [Presentation] U-PA PLAYS A CRITICAL ROLE IN THE INDUCTION OF MACROPHAGE POLARITY DURING LIVER REPAIR (2012)
  • Author(s): Naoyuki Kawao et al.
  • Organizer: 21st International Congress on Fibrinolysis & Proteolysis
  • Place of Presentation: Brighton UK
• [Presentation] 肝修復過程におけるu-PAによるマクロファージの機能制御 (2012)
  • Author(s): 河尾直之 他
  • Organizer: 第34回日本血栓止血学会学術集会
  • Place of Presentation: 東京都、ハイアットリージェンシー東京
• [Presentation] Macrophages are regulated by urokinase-type plasminogen activator during liver repair (2012)
  • Author(s): 河尾直之 他
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場（京都府）
• [Presentation] Roles of urokinase-type plasminogen activator and plasminogen in both accumulation of macrophages and induction of their phenotype heterogeneity during liver repair (2012)
  • Author(s): 河尾直之 他
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野県松本文化会館（長野県）
• [Presentation] 肝障害部位へのマクロファージの集積および活性化におけるu-PAの役割 (2011)
  • Author(s): 河尾直之, 永井信夫,田村行識,奥本勝美,岡田清孝,矢野昌人,鈴木康裕,梅村和夫,梶 博史,松尾 理
  • Organizer: 第61回日本薬学会近畿支部大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2011-10-22
• [Presentation] Impaired accumulation of macrophages and absence of their phenotype heterogeneity during liver repair in urokinase-deficient mice (2011)
  • Author(s): Kawao N, Nagai N, Tamura Y, Okumoto K, Okada K, Yano M, Suzuki Y, Umemura K, Ueshima S, Matsuo O.
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: 京都府京都市
• [Presentation] Urokinase-type plasminogen activator and plasminogen mediate accumulation of macrophages and their phenotype heterogeneity at the border region of damaged site during liver repair (2011)
  • Author(s): Kawao N, Nagai N, Tamura Y, Okumoto K, Okada K, Yano M, Suzuki Y, Umemura K, Ueshima S, Kaji H, Matsuo O.
  • Organizer: The 76th Japanese Society of Interferon & Cytokine Research The 19th International Symposium on Molecular Cell Biology of Macrophages.
  • Place of Presentation: 大阪府泉佐野市
• [Presentation] Urokinase-type plasminogen activator and plasminogen mediate accumulation of macrophages and their phenotype heterogeneity at the border region of damaged site during liver repair (2011)
  • Author(s): Naoyuki Kawao 他
  • Organizer: The 76th Japanese Society of Interferon & Cytokine Research The 19th International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: ANAゲートタワーホテル（大阪府）
• [Presentation] Impaired accumulation of macrophages and absence of their phenotype heterogeneity during liver repair in urokinase-deficient mice (2011)
  • Author(s): Naoyuki Kawao 他
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: 京都国際会議場（京都府）
• [Presentation] Role of plasminogen in liver repair (2011)
  • Author(s): Osamu Matsuo 他
  • Organizer: 6th Japanese-German Conference on Thrombosis and Hemostasis(招待講演)
  • Place of Presentation: 札幌
• [Presentation] 肝障害部位へのマクロファージの集積および活性化におけるu-PAの役割 (2011)
  • Author(s): 河尾直之 他
  • Organizer: 第61回日本薬学会近畿支部大会
  • Place of Presentation: 神戸学院大学（兵庫県）
• [Remarks]
  • URL: http://www.med.kindai.ac.jp/physio2/
• [Remarks] 近畿大学医学部再生機能医学講座
  • URL: http://www.med.kindai.ac.jp/physio2/