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TGFb signaling pathways involved in rupture of aortic aneurysms

Research Project

Project/Area Number 15K20898
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Cardiovascular medicine
Research InstitutionUniversity of Tsukuba

Principal Investigator

YAMASHIRO Yoshito  筑波大学, 生命領域学際研究センター, 助教 (70751923)

Research Collaborator Yanagisawa Hiromi  筑波大学, 生命領域学際研究センター, 教授 (40746301)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords大動脈瘤 / TGFβ / メカニカルストレス / 大動脈瘤破裂 / TGF-β / 血管平滑筋細胞 / 細胞外マトリックス
Outline of Final Research Achievements

In the Fbln4SMKO (mice model for ascending aortic aneurysm; SMKO) mice, treatment with TGF-β neutralizing antibody (1D11) leads to aneurysm rupture. We examined conditions for 1D11 treatment and signaling pathways involved in aneurysm rupture in SMKO mice. First, We considered concentration, administration period for 1D11 treatment and finally established suitable conditions for 1D11 treatment leadding rupture. In addition, we found that the expression of ACE (angiotensin converting enzyme), Egr1 (Early growth response-1) and Thrombospondin-1 increased in ascending aorta after TAC procedure, which enhanced mechanical stress in the aorta. Thus, we denied these molecules as mechanical stress response factor and hypothesized that mechanical stress response factor might involved in aneurysm initiation.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Remarks (4 results)

  • [Int'l Joint Research] UT Southwestern Medical Center/University of Washington, St. Louis(米国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] McGill University(Canada)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Abnormal mechanosensing and cofilin activation promotes the progression of ascending aortic aneurysms in mice2015

    • Author(s)
      Y. Yamashiro, C. L. Papke, J. Kim, L.-J. Ringuette, Q.-J. Zhang, Z.-P. Liu, H. Mirzaei, J. E. Wagenseil, E. C. Davis, and H. Yanagisawa
    • Journal Title

      Science Signaling

      Volume: 8(399) Issue: 399

    • DOI

      10.1126/scisignal.aab3141

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Loss of fibulin-4 disrupts collagen synthesis and maturation: Implications for pathology resulting from EFEMP2 mutations2015

    • Author(s)
      C. L. Papke, J. Tsunezumi, L.-J. Ringuette, H. Nagaoka, M. Terajima, Y. Yamashiro, G. Urquhart, M. Yamauchi, E. C. Davis, and H. Yanagisawa
    • Journal Title

      Human Molecular Genetics

      Volume: 15;24(20) Issue: 20 Pages: 5867-79

    • DOI

      10.1093/hmg/ddv308

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] MMP17/MT4-MMP and thoracic aortic aneurysms: OPNing new potential for effective treatment2015

    • Author(s)
      C. L. Papke, Y. Yamashiro, and H. Yanagisawa
    • Journal Title

      Circulation Research

      Volume: 117 Pages: 109-112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Abnormal mechanosensing underling aortic aneurysm formation2016

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      Molecular Cardiovascular Conference II
    • Place of Presentation
      東京ドームホテル(東京都・文京区)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Abnormal Mechanosensing underling ascending aneurysm formation2016

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      第48回日本結合組織学会
    • Place of Presentation
      長崎大学医学部(長崎県・長崎市)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Vessel wall integrity under the mechanical stress2016

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      日本血管生物医学会若手の会
    • Place of Presentation
      東北大学 加齢医学研究所(仙台)
    • Year and Date
      2016-03-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Abnormal mechanosensing and cofilin activation promotes the progression of ascending aortic aneurysm in mice2015

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      日本血管生物医学会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Abnormal mechanosensing and cofilin activation promotes the progression of ascending aortic aneurysm in mice2015

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      エラスチン研究会
    • Place of Presentation
      私学会館アルカディア市ヶ谷(東京)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Abnormal mechanosensing and cofilin activation promotes the progression of ascending aortic aneurysm in mice2015

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      大動脈病態研究会
    • Place of Presentation
      久留米大学(福岡)
    • Year and Date
      2015-08-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Abnormal mechanosensing and cofilin activation promotes the progression of ascending aortic aneurysm in mice2015

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      ニューイングランド大学(メイン州、U.S.A)
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Abnormal mechanosensing and activation of slingshot-cofilin pathway underlie initiation and expansion of ascending aortic aneurysms in fibulin-4 deficient mice2015

    • Author(s)
      Yoshito Yamashiro
    • Organizer
      日本細胞生物学会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 筑波大学 生命領域学際研究センター

    • URL

      http://saggymouse.tara.tsukuba.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 筑波大学 生命領域学際研究センター 柳沢裕美研究室

    • URL

      http://saggymouse.tara.tsukuba.ac.jp/

    • Related Report
      2015 Research-status Report
  • [Remarks] 筑波大学 公式サイト 注目の研究

    • URL

      http://www.tsukuba.ac.jp/attention-research/p201510210300.html

    • Related Report
      2015 Research-status Report
  • [Remarks] Science Signaling 論文掲載ページ

    • URL

      http://stke.sciencemag.org/content/8/399/ra105.full

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-01-27  

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