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Molecular pathological examination of valvulitis developed in TAX1BP1 deficient mice.

Research Project

Project/Area Number 22590364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOita University

Principal Investigator

IHA Hidekatsu  大分大学, 医学部, 准教授 (50242631)

Co-Investigator(Kenkyū-buntansha) TSUKAMOTO Yoshiyuki  大分大学, 医学部, 助教 (00433053)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsTAX1BP1 / 心弁膜炎 / IL-6 / KC / TAX1BP1-KO / 慢性炎症 / 自然免疫 / 心機能 / アレイ解析 / SAA3 / I-κBα / KC(CXCL-1)
Research Abstract

Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules with its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3) exhibited a 1,180-fold induction (FI), CHI3L1(361-FI), HP(187-FI), IL1B(122-FI) and SPP1/OPN(101-FI). WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation in the area. Antibiotics-induced ‘germ free’ status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice’s inflammatory lesions. These pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (20 results)

All 2013 2012 2011 2010 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (16 results) Book (1 results) Remarks (1 results)

  • [Journal Article] MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC22013

    • Author(s)
      Matsuo M, Nakada C, Tsukamoto Y, Noguchi T, Uchida T, Hijiya N, Matsuura K, Moriyama M
    • Journal Title

      Mol Cancer

      Volume: 12 Issue: 1 Pages: 15-15

    • DOI

      10.1186/1476-4598-12-15

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization2011

    • Author(s)
      Kuroda A, Tsukamoto Y, Nguyen LT, Noguchi T, Takeuchi I, Uchida M, Uchida T, Hijiya N, Nakada C, Okimoto T, Kodama M, Murakami K, Matsuura K, Seto M, Ito H, Fujioka T, Moriyama M
    • Journal Title

      PLoS One

      Volume: 6(7) Pages: 22313-22313

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] TAX1BP1 欠損マウスが形成する自己免疫病態 および心機能不全は常在細菌によってもたらされる2012

    • Author(s)
      伊波英克他
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場、福岡
    • Year and Date
      2012-12-11
    • Related Report
      2012 Final Research Report
  • [Presentation] TAX1BP1-deficiency evokes spatiotemporal development of systemic inflammatory symptoms andfunctional failures of cardiovascularsystem in mice2012

    • Author(s)
      伊波英克他
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ、千葉
    • Year and Date
      2012-12-05
    • Related Report
      2012 Final Research Report
  • [Presentation] ATL 細胞における Tax1bp1 の過剰異所性発現2012

    • Author(s)
      伊波英克他
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2012-11-13
    • Related Report
      2012 Final Research Report
  • [Presentation] TAX1BP1-deficiency evokes spaciotemporal development of inflammatory symptoms and functional failures in the murine cardiac system2012

    • Author(s)
      Satoko Nakano, 他11名
    • Organizer
      「修飾シグナル病」第二回公開シンポジウム
    • Place of Presentation
      東京大学医科学研究所
    • Year and Date
      2012-01-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] ATL細胞におけるTax1bp1の過剰異所性発現2012

    • Author(s)
      伊波 英克
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] TAX1BP1-deficiency evokes spatiotemporal development of systemic inflammatory symptoms and functional failures of cardiovascular system in mice2012

    • Author(s)
      伊波 英克
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] TAX1BP1欠損マウスが形成する自己免疫病態 および心機能不全は常在細菌によってもたらされる2012

    • Author(s)
      伊波 英克
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      マリンメッセ福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] TAX1BP1-deficiency evokes spaciotemporal development of inflammatory symptoms and functional failures in the murine cardiac system2011

    • Author(s)
      伊波英克他
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場、兵庫
    • Year and Date
      2011-11-29
    • Related Report
      2012 Final Research Report
  • [Presentation] TAX1BP1-deficiency evokes spaciotemporal development of inflammatory symptoms and functional failures in the murine cardiac system2011

    • Author(s)
      Satoko Nakano, 他11名
    • Organizer
      日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] TAX1BP1 遺伝子欠損は全身性の炎症亢進と心機能不全を誘発する2011

    • Author(s)
      伊波英克他
    • Organizer
      第18回MPO 研究会
    • Place of Presentation
      京都大学紫蘭会館別館、京都
    • Year and Date
      2011-10-28
    • Related Report
      2012 Final Research Report
  • [Presentation] TAX1BP1遺伝子欠損は全身性の炎症亢進と心機能不全を誘発する2011

    • Author(s)
      伊波英克, 他13名
    • Organizer
      MPO研究会
    • Place of Presentation
      アークホテル熊本
    • Year and Date
      2011-10-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tax1-bp1 欠損マウスは時空間的に全身炎症を発生し、その心弁膜炎症は心機能不全をもたらす2011

    • Author(s)
      伊波英克他
    • Organizer
      第5回 HTLV -1 研究会
    • Place of Presentation
      東京大学医科学研究所、東京
    • Year and Date
      2011-09-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Tax1-bp1欠損マウスは時空間的に全身炎症を発生し、その心弁膜炎症は心機能不全をもたらす2011

    • Author(s)
      中野聡子, 他13名
    • Organizer
      HTLV-1研究会
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2011-09-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 「Tax1bp1 欠損マウス」を用いたエンドトキシン誘発ぶどう膜炎の解析2011

    • Author(s)
      中野聡子、伊波英克他
    • Organizer
      第45回日本眼炎症学会学術集会
    • Place of Presentation
      京王プラザホテル、東京
    • Year and Date
      2011-07-10
    • Related Report
      2012 Final Research Report
  • [Presentation] 「Tax1bp1欠損マウス」を用いたエンドトキシン誘発ぶどう膜炎の解析2011

    • Author(s)
      中野聡子, 他6名
    • Organizer
      日本眼炎症学会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2011-07-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 慢性炎症病態を形成するTax1bp1-KOマウスにおけるLPS誘導性急性期炎症反応2010

    • Author(s)
      中野聡子
    • Organizer
      日本分子生物学会
    • Place of Presentation
      ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Book] Glycan Profiling of Adult T-Cell Leukemia (ATL) Cells with the High Resolution Lectin Microarrays2012

    • Author(s)
      Iha h, Yamada M
    • Publisher
      T-Cell Leukemia -Characteristics, Treatment and Prevention
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.med.oita-u.ac.jp/biseibut/HIHA/HIHA_Home/Index.html

    • Related Report
      2012 Final Research Report

URL: 

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

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