Identification of the transcriptional active region of the genome in autoimmune diseases.

自身免疫性疾病基因组转录活性区域的鉴定。

基本信息

  • 批准号:
    14570407
  • 负责人:
  • 金额:
    $ 1.86万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2003
  • 项目状态:
    已结题

项目摘要

Human endogenous retrovirus (HERV) sequences are dispersed throughout the genome, which are thus considered to be a useful genetic marker for genome research. HERVs may participate in the pathogenesis of autoimmunity, via the formation of immune complexes after translation, or activation of the surrounding genes via their promoter /enhancer activity. The demethylation of cytosine at the CpG islands is associated with transcriptional activity In this study, the profile of CAN methylation around the hhh s were examined by suppression ppp. Adapter primer was added to the genomic ddd, which was degested with methylation-sensitive restriction enzyme(HpaII). Suppression ppp was subsequently performed tor ampligy the HpaII fragments containing hhh sequences, using the primer for adapter sequence, and the fluorescence-labeled primer comon to the various hhh sss (U5 and U3 region ). S control, metylation-insensitve restriction enzyme(MspI) was used, and the length of fragments was analyzed by a … More utomatic sssr. The profile of suppression ppp using HpaII fragments as template was different between neutrophils and and lymph nodes. In contrast the profile using MspI fragments as template was identical. Therefore, it is considered that the different profile of suppression ppp may result from the methylation-status (epigenetic) defference among the tissues. As to rheumatoid arthritis (RA),PADI4 was demonstrated to be in RA, although the relevance of its methylation was unknown. On the other hand, NF-kB inhibitors was also investigated. Among the chemicals, designed via computere-assisted drug design, the compound was selected as most effective inhibitor of transcriptional NF-kB activity, the proliferation and the production of proinflammatory cytokines from synovial cell lines. The compund was effective in mouse collagen artrits model at a dosage of 1-3mg/kg, shich is promising as novel anti-rheumatic therapy, although further study investigating its safety profile is necessary. The effect of this compund on the methylation profile around perform for the analysis of the entire profile of methylation, it would be useful for the investigation of epigenetic factor (methylation status) of genome DNA in various autoimmune diseases. Less
人类内源性逆转录病毒(HERV)序列广泛分布于基因组中,被认为是基因组研究中有用的遗传标记。HERV可能通过翻译后形成免疫复合体或通过其启动子/增强子活性激活周围基因而参与自身免疫的发病。胞嘧啶在CpG岛上的去甲基化与转录活性有关。在本研究中,用抑制PPP法检测了S HHH周围CaN甲基化的情况。在基因组DDD中加入适配引物,用甲基化敏感限制性内切酶(HpaII)脱酶。随后使用适配序列的引物和不同的HHH SSs(U5和U3区)上的荧光标记引物,对包含HHH序列的HpaII片段进行抑制PPP。以S为对照,用甲基化无感觉限制性内切酶(MSPI)扩增DNA片段,用…方法分析片段长度更自动的SSSR。以HpaII片段为模板的抑制PPP在中性粒细胞和淋巴结中的表达谱不同。相反,使用MspI片段作为模板的图谱是相同的。因此,认为抑制PPP的不同图谱可能是由于组织间甲基化状态(表观遗传)的差异所致。在类风湿关节炎(RA)中,PADI4基因被证实存在于类风湿关节炎中,但其甲基化的相关性尚不清楚。另一方面,对核因子-kB抑制剂也进行了研究。在通过计算机辅助药物设计设计的化学物质中,该化合物被选为最有效的抑制滑膜细胞系转录核因子-kB活性、增殖和产生促炎细胞因子的抑制剂。该制剂在1~3 mg/kg的剂量范围内对小鼠胶原性关节炎模型有较好的疗效,有希望成为一种新型的抗风湿药物,但其安全性有待进一步研究。对于甲基化全过程的分析,它将有助于研究各种自身免疫性疾病中基因组DNA的表观遗传因素(甲基化状态)。较少

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Suzuki K, Sawada T et al.: "High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis."Scandinavian Journal of Rheumatology. 32・4. 197-204 (2003)
Suzuki K、Sawada T 等人:“类风湿性关节炎中瓜氨酸抗原抗体的 ELISA 检测具有高诊断性能。”斯堪的纳维亚风湿病学杂志 32·4 (2003)。
  • DOI:
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  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Suzuki A et al.: "Functional haplotypes of PADI4,encoding citrullinating enzyme peptidylarginine deiminase 4,are associated with rheumatoid arthritis."Nature Genetics. 34・4. 395-402 (2003)
Suzuki A 等人:“编码瓜氨酸酶肽酰精氨酸脱亚胺酶 4 的 PADI4 的功能单倍型与类风湿性关节炎有关。”《自然遗传学》34·4 (2003)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
沢田哲治: "関節炎重症例の薬物治療の実際"Medical Practice. 19巻7号. 1189-1193 (2002)
Tetsuji Sawada:“关节炎严重病例的药物治疗实践”,第 19 卷,第 7 期。1189-1193 (2002)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Suzuki A et al.: "functional haplytypes of PADI4,encoding citrullinating enzyme peptidylarginine deiminase4, are associated with rheumatoid arthritis."Nature Genetics. 32(4). 395-402 (2003)
Suzuki A 等人:“PADI4 的功能性单倍型编码瓜氨酸酶肽酰精氨酸脱亚胺酶 4,与类风湿性关节炎相关。”《自然遗传学》。
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    0
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SAWADA Tetsuji其他文献

SAWADA Tetsuji的其他文献

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{{ truncateString('SAWADA Tetsuji', 18)}}的其他基金

Identification of novel citrullinated antigen of RA, prospects for the pathogenesis of rheumamtoid arthritis and biomarkers
RA新型瓜氨酸抗原的鉴定、类风湿性关节炎发病机制及生物标志物的展望
  • 批准号:
    22591086
  • 财政年份:
    2010
  • 资助金额:
    $ 1.86万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of novel citrullinated antigens in rheumatoid arthritis (RA) and the role of anti-CCP antibody in the pathogenesis of RA
类风湿性关节炎 (RA) 中新型瓜氨酸抗原的鉴定以及抗 CCP 抗体在 RA 发病机制中的作用
  • 批准号:
    17591033
  • 财政年份:
    2005
  • 资助金额:
    $ 1.86万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
New strategy for pancreatic cancer. immunotargeting therapy by chimeric monoclonal antibody
胰腺癌的新策略。
  • 批准号:
    13671330
  • 财政年份:
    2001
  • 资助金额:
    $ 1.86万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
THE ROLE OF IMMUNE SYSTEM AND DIFFERENTIATION AT MICROENVIRNMENT INVOLVED IN INVASION AND METASTASIS OF PANCREATIC CANCER
免疫系统及微环境分化在胰腺癌侵袭转移中的作用
  • 批准号:
    08671475
  • 财政年份:
    1996
  • 资助金额:
    $ 1.86万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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用于社区主导的定制牲畜 DNA 甲基化阵列开发的模块化工作流程
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