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

2012 Fiscal Year Final Research Report

• 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
• Keywords: 肝修復 / マクロファージ / 組織線溶系

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 ischemia and stroke. (2012)
  • Author(s): ayasaka N, Nagai N, Kawao N, Niwa A, Yoshioka Y, Mori Y, Shigeta H, Kashiwagi N, Miyazawa M, Satou T, Higashino H, Matsuo O, Murakami T.
  • Journal Title: PLoS One. Volume: 7 Pages: e32342
  • DOI: 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 Pages: 749-59
  • DOI: 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 Pages: 424-7
  • DOI: doi:10.1097/WNR.0b013e3283462dd9.
  • Peer Reviewed
• [Journal Article] A synthetic peptide derived from staphylokinase enhances plasminogen activation 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 Pages: 997-1006
  • DOI: doi:10.1111/j.1538-7836.2011.04257.x.
  • Peer Reviewed
• [Journal Article] Urokinase-type plasminogen activator contributes to heterogeneity of macrophages at the border of damaged site during liver repair in mice. (2011)
  • 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 Pages: 892-900
  • DOI: doi:10.1160/TH10-08-0516.
  • 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, Kawao N, Yano M, Ueshima S, Nagai N, Matsuo O.
  • Journal Title: J Thromb Thrombolysis. Volume: 32 Pages: 195-200
  • DOI: doi:10.1007/s11239-011-0552-2.
  • Peer Reviewed
• [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
  • Year and Date: 20120701-05
• [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
  • Year and Date: 20120607-09
• [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
  • Year and Date: 20120329-31
• [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
  • Year and Date: 20120314-16
• [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
  • Year and Date: 20110723-28
• [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
  • Year and Date: 20110525-27
• [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
• [Remarks]
  • URL: http://www.med.kindai.ac.jp/physio2/