Molecular pathological examination of valvulitis developed in TAX1BP1 deficient mice.

TAX1BP1 缺陷小鼠发生瓣膜炎的分子病理学检查。

• 批准号: 22590364
• 负责人: IHA Hidekatsu
• 金额: $ 2.91万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590364/
• 关键词: 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)

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.

Tax 1结合蛋白1（Tax 1bp 1）通过与其催化配偶体A20编辑靶分子的泛素化来负调控NF-κB。基因工程TAX 1BP 1缺陷（KO）小鼠在多个器官中发展出年龄依赖性炎症结构，表现为瓣膜炎或皮炎，并过早死亡。对TAX 1BP 1-KO小鼠（8周龄和16周龄）的二尖瓣进行激光捕获解剖和基因表达微阵列分析，发现与野生型相比有588个基因转录改变。SAA 3（血清淀粉样蛋白A3）表现出1，180倍诱导（FI），CHI 3L 1（361-FI），HP（187-FI），IL 1B（122-FI）和SPP 1/OPN（101-FI）。WIF 1（Wnt抑制因子1）表现出11倍的减少。再次证实了强烈的Saa 3染色和显著的I-κBα减少，以及该区域大量炎性淋巴细胞浸润和水肿形成。抗生素诱导的“无菌”状态或额外的MyD 88缺陷显著改善了TAX 1BP 1-KO小鼠的炎症病变。这些病理状况，我们称之为“假感染性心内膜炎”，是由共生微生物群加剧的，而共生微生物群通常本质上是无害的。这一实验结果提出了一种新的机制之间的联系，内皮炎症引起的泛素重塑免疫调节剂和致命的心功能不全。

项目成果

TAX1BP1-deficiency evokes spatiotemporal development of systemic inflammatory symptoms and functional failures of cardiovascular system in mice

TAX1BP1缺陷会引起小鼠全身炎症症状和心血管系统功能衰竭的时空发展

• 发表时间: 2012
• 作者: 柿崎正敏;ほか;久保秀司;John A.Mengshol;Yasuo Ouchi;伊波 英克
• 通讯作者: 伊波 英克

MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2.

miR-29c在胃癌中被下调，并通过靶向RCC2来调节细胞增殖。

• DOI: 10.1186/1476-4598-12-15
• 发表时间: 2013-02-25
• 期刊: Molecular cancer
• 影响因子: 37.3
• 作者: Matsuo M;Nakada C;Tsukamoto Y;Noguchi T;Uchida T;Hijiya N;Matsuura K;Moriyama M
• 通讯作者: Moriyama M

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

Tax1-bp1缺陷小鼠会出现时空全身炎症，而瓣膜炎症会导致心脏功能障碍。

• 发表时间: 2011
• 作者: R.Watanabe;H.Kashiwazaki;門脇健;Takeshi Udagawa;伊波英克他
• 通讯作者: 伊波英克他

TAX1BP1-deficiency evokes spatiotemporal development of systemic inflammatory symptoms andfunctional failures of cardiovascularsystem in mice

TAX1BP1缺陷引起小鼠全身炎症症状和心血管系统功能衰竭的时空发展

• 发表时间: 2012
• 作者: Takaoka Y.;Shimizu Y.;Hasegawa H.;Ouchi Y.;Qiao S.;Nagahara M.;Ichihara M.;Lee J.D.;Adachi K.;Hamaguchi M.;Iwamoto T.;柏崎広美;伊波英克他
• 通讯作者: 伊波英克他

「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

使用“Tax1bp1缺陷小鼠”分析内毒素诱发的葡萄膜炎

• 发表时间: 2011
• 作者: 中野聡子;伊波英克他
• 通讯作者: 伊波英克他