Molecular pathological examination of valvulitis developed in TAX1BP1 deficient mice.
| Project/Area Number |
22590364
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAMOTO Yoshiyuki 大分大学, 医学部, 助教 (00433053)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| 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)
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| Keywords | TAX1BP1 / 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) |
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| 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.
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Report
(4 results)
Research Products
(20 results)
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[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
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Journal Title
PLoS One
Volume: 6(7)
Pages: 22313-22313
Related Report
Peer Reviewed
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