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KLF network in chronic diseases and cancer

Research Project

Project/Area Number 22229006
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

NAGAI Ryozo  東京大学, 医学部附属病院, 名誉教授 (60207975)

Co-Investigator(Kenkyū-buntansha) MANABE Ichiro  東京大学, 医学部附属病院, 講師 (70359628)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥217,620,000 (Direct Cost: ¥167,400,000、Indirect Cost: ¥50,220,000)
Fiscal Year 2014: ¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2013: ¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2012: ¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2011: ¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2010: ¥44,200,000 (Direct Cost: ¥34,000,000、Indirect Cost: ¥10,200,000)
Keywords転写因子 / 動脈硬化 / 糖尿病 / 慢性腎臓病 / 心不全 / メタボリックシンドローム / がん
Outline of Final Research Achievements

The Kruppel-like factor family consists of 17 zinc-finger-type transcription factors. This project aimed to elucidate pathological roles of KLF5 and KLF6 in cardiovascular, metabolic, and renal diseases and cancer. We found that KLF6 expressed in cardiomyocytes and KLF5 expressed in cardiac fibroblasts control cardiac responses to stress, such as cardiac hypertrophy and fibrosis. KLF6 is also important for controlling aortic inflammation. In kidneys KLF5 controls renal inflammation, which underlies chronic kidney disease. KLF5 also control intestinal stem cell function and associates with colon cancer. The mechanisms and pathways identified in this project would be attractive targets for the development of new therapeutic and diagnostic strategies.

Assessment Rating
Verification Result (Rating)

A-

Assessment Rating
Result (Rating)

A: Progress in the research is steadily towards the initial goal. Expected research results are expected.

Report

(9 results)
  • 2015 Research Progress Assessment (Verification Result) ( PDF )
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (18 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (5 results) (of which Invited: 3 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma2015

    • Author(s)
      Son, BK
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 6994-6994

    • DOI

      10.1038/ncomms7994

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells2014

    • Author(s)
      Nakaya, T
    • Journal Title

      Cancer Res

      Volume: 74 Issue: 10 Pages: 2882-2891

    • DOI

      10.1158/0008-5472.can-13-2574

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis2014

    • Author(s)
      Noda, S
    • Journal Title

      Nat Commun

      Volume: 5 Issue: 1 Pages: 5797-5797

    • DOI

      10.1038/ncomms6797

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lineage of Bone Marrow–Derived Cells in Atherosclerosis.2013

    • Author(s)
      Iwata H
    • Journal Title

      Circulation Research

      Volume: 112 Issue: 12 Pages: 1634-1647

    • DOI

      10.1161/circresaha.113.301384

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Saturated fatty acid palmitate aggravates neointima formation by promoting smooth muscle phenotypic modulation2013

    • Author(s)
      Shen H
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 33 Issue: 11 Pages: 2596

    • DOI

      10.1161/atvbaha.113.302099

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Post-transcriptional activation of PPAR alpha by KLF6 in hepatic steatosis.2013

    • Author(s)
      Bechmann LP
    • Journal Title

      Journal of Hepatology

      Volume: in press Issue: 5 Pages: 1000-1006

    • DOI

      10.1016/j.jhep.2013.01.020

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Saturated fatty acid and TLR signaling link β cell dysfunction and islet inflammation.2012

    • Author(s)
      Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R
    • Journal Title

      Cell Metab.

      Volume: 15 Issue: 4 Pages: 518-533

    • DOI

      10.1016/j.cmet.2012.01.023

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Renal collecting duct epithelial cells regulate inflammation in tubulointerstitial damage in mice2011

    • Author(s)
      Fujiu K
    • Journal Title

      Journal of Clinical Investigation

      Volume: 121 Issue: 9 Pages: 3425-3441

    • DOI

      10.1172/jci57582

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory polymorphism in transcription factor KLF5 at the MEF2 element alters the response to angiotensin II and is associated with human hypertension2010

    • Author(s)
      Oishi Y
    • Journal Title

      FASEB J

      Volume: 24 Pages: 1780-1788

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages2010

    • Author(s)
      Iwata H
    • Journal Title

      Circulation

      Volume: 122 Pages: 2048-2057

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 心血管代謝疾患の病態形成と慢性炎症2013

    • Author(s)
      永井良三
    • Organizer
      第60回日本臨床検査医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2013-11-01
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 慢性炎症と病態形成2013

    • Author(s)
      永井良三
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2013-04-06
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Chronic Inflammatory Response in Cardiovascular Remodeling and in Metabolic Syndrome2011

    • Author(s)
      Nagai R
    • Organizer
      AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      東京
    • Year and Date
      2011-12-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Kruppel-like factor 5 and cardiovascular system : from transcriptional regulator to therapeutic target2010

    • Author(s)
      Nagai R
    • Organizer
      2010 FASEB summer research conference
    • Place of Presentation
      Steamboat Springs、米国
    • Year and Date
      2010-08-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Chronic inflammatory response in cardio-vascular remodeling, metabolic syndrome and cardiorenal syndrome

    • Author(s)
      Nagai R
    • Organizer
      第20回日本血管生物医学会学術集会
    • Place of Presentation
      徳島
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] 臓器円環による生体恒常性のダイナミクス2013

    • Author(s)
      永井良三
    • Total Pages
      222
    • Publisher
      羊土社
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/nagai

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] リンパ浮腫の治療法2010

    • Inventor(s)
      永井良三, 他
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Number
      2010-226603
    • Filing Date
      2010-10-06
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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