Significance of differentially expressed microRNAs and their target proteins in the development of autoimmune myocarditis in mouse model and patients

差异表达的microRNA及其靶蛋白在小鼠模型和患者自身免疫性心肌炎发生中的意义

基本信息

项目摘要

Causes for a predisposition for an autoimmune myocarditis in patients as well as animals are still unknown. It has been shown that some mouse strains (A/J and BALB/C) are susceptible to the induction of an experimental autoimmune myocarditis and some are not (C57BL/6). In preliminary studies, we could identify a potential involvement of differentially expressed microRNA (miRs), small non-coding oligoribonucleotides, in the predisposition for an autoimmune myocarditis. The aim of our study is to elucidate the mechanisms involved in the different susceptibility to an autoimmune myocarditis and identify novel therapeutic targets. In this study, we will analyze the role of miRs upregulated in the C57BL/6 strain. Since miR-34a-5p and miR-135a-5p appear to be protective in these mice we will study how inhibiting these miRs in C57BL/6 mice affect the susceptibility to autoimmune myocarditis. Furthermore, we will analyze if the overexpression of these miRs via AAV9-vectors in the hearts of A/J- as well as BALB/C-mice will be protective. Finally, the role of target proteins of these miRs such as PNUTS in the disposition for an autoimmune myocarditis will be evaluated. In a further approach, we will investigate if treating animals with miR inhibitors against miRs upregulated in our model of autoimmune myocarditis such as miR-21a-5p or miR-146b-5p will reduce or inhibit an inflammation. Moreover, novel signaling pathways associated with these miRs will be investigated. In particular, we will analyze if the overexpression of selected target proteins (e.g. IRAK1, TRAF6, ERK1/2, Sprouty 1) with AAV9-vectors will be able to prevent an EAM. In a last step, we will investigate if the miR-expression profile of susceptible mice after TnI immunization correlates with the miR-expression profils of patients analyzed in blood samples and heart biopsies. These analyses should enable novel insights in the susceptibility to autoimmune myocarditis in humans and result in identification of novel therapeutic targets.
在患者和动物中易患自身免疫性心肌炎的原因仍然未知。已表明,一些小鼠品系(A/J和BALB/C)对诱导实验性自身免疫性心肌炎敏感,而一些小鼠品系(C57 BL/6)则不敏感。在初步研究中,我们可以确定差异表达的microRNA(miR),小的非编码寡核苷酸,在自身免疫性心肌炎的易感性的潜在参与。本研究的目的是阐明自身免疫性心肌炎易感性不同的机制,并确定新的治疗靶点。在这项研究中,我们将分析C57 BL/6菌株中miR上调的作用。由于miR-34 a-5 p和miR-135 a-5 p在这些小鼠中似乎具有保护作用,我们将研究在C57 BL/6小鼠中抑制这些miR如何影响对自身免疫性心肌炎的易感性。此外,我们将分析这些miR通过AAV 9载体在A/J-以及BALB/C-小鼠心脏中的过表达是否具有保护性。最后,将评估这些miR的靶蛋白如PNUTS在自身免疫性心肌炎的处置中的作用。在进一步的方法中,我们将研究用针对在我们的自身免疫性心肌炎模型中上调的miR(例如miR-21 a-5 p或miR-146 b-5 p)的miR抑制剂治疗动物是否会减少或抑制炎症。此外,与这些miR相关的新的信号通路将被研究。特别地,我们将分析用AAV 9载体过表达选定的靶蛋白(例如IRAK 1,TRAF 6,ERK 1/2,Sprouty 1)是否能够预防EAM。在最后一步中,我们将研究TnI免疫后易感小鼠的miR表达谱是否与血液样本和心脏活检中分析的患者的miR表达谱相关。这些分析应使新的见解在人类自身免疫性心肌炎的易感性,并导致新的治疗靶点的识别。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Professor Dr. Ziya Kaya其他文献

Professor Dr. Ziya Kaya的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Professor Dr. Ziya Kaya', 18)}}的其他基金

Role of regulatory B-cells in pathogenesis and progression of autoimmune myocarditis
调节性 B 细胞在自身免疫性心肌炎发病机制和进展中的作用
  • 批准号:
    317530962
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Interleukin-10 mRNA-Transfektion von Makrophagen zur antiinflammatorischen Therapie - proof of principle am Myokarditis- Modell der Maus
Interleukin-10 mRNA 转染巨噬细胞进行抗炎治疗 - 小鼠心肌炎模型的原理证明
  • 批准号:
    188218526
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Identifizierung der für die Induktion von Herzmuskelentzündung verantwortlichen Epitope des kardialen Troponins I und Toleranzinduktion als Therapieansatz
鉴定负责诱导心肌炎和耐受诱导作为治疗方法的心肌肌钙蛋白 I 表位
  • 批准号:
    58918522
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Untersuchungen zur Induktion einer Autoimmunreaktion auf zirkulierendes kardiales Troponin nach Myokardinfarkt und ihre klinische Bedeutung
心肌梗死后循环心肌肌钙蛋白诱导自身免疫反应的研究及其临床意义
  • 批准号:
    18879691
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Funktionelle Untersuchungen zur Beteiligung von Komplement/Komplementrezeptoren in der Pathogenese der Myokarditis
补体/补体受体参与心肌炎发病机制的功能研究
  • 批准号:
    5414334
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:
    Research Grants

相似海外基金

Algorithm development for detecting differentially expressed genes in single-cell RNA-seq
检测单细胞 RNA-seq 中差异表达基因的算法开发
  • 批准号:
    21K15078
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Epigenetic Regulation of Differentially Expressed Genes in Cutaneous T Cell Lymphoma
皮肤T细胞淋巴瘤差异表达基因的表观遗传调控
  • 批准号:
    10467983
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Epigenetic Regulation of Differentially Expressed Genes in Cutaneous T Cell Lymphoma
皮肤T细胞淋巴瘤差异表达基因的表观遗传调控
  • 批准号:
    10490348
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Epigenetic Regulation of Differentially Expressed Genes in Cutaneous T Cell Lymphoma
皮肤T细胞淋巴瘤差异表达基因的表观遗传调控
  • 批准号:
    10015553
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Epigenetic Regulation of Differentially Expressed Genes in Cutaneous T Cell Lymphoma
皮肤T细胞淋巴瘤差异表达基因的表观遗传调控
  • 批准号:
    10657598
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Differentially expressed genes analysis by RNA-seq : Inflamed periodontal tissue of ligature-induced periodontitis in mice
RNA-seq差异表达基因分析:小鼠结扎诱发牙周炎的发炎牙周组织
  • 批准号:
    17K17348
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Functional analysis of differentially expressed genes contributing to insect freeze tolerance
昆虫耐冻性差异表达基因的功能分析
  • 批准号:
    459162-2014
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Functional analysis of differentially expressed genes contributing to insect freeze tolerance
昆虫耐冻性差异表达基因的功能分析
  • 批准号:
    459162-2014
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Functional analysis of differentially expressed genes contributing to insect freeze tolerance
昆虫耐冻性差异表达基因的功能分析
  • 批准号:
    459162-2014
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Identifying novel angiogenesis-related pathway from differentially expressed genes during retinal development obtained by the microarray analysis
通过微阵列分析获得的视网膜发育过程中差异表达基因鉴定新的血管生成相关途径
  • 批准号:
    26460395
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了