长链非编码RNA uc008ppm.1作为抗心肌纤维化治疗靶点的潜能和调控机理研究

批准号:
81970223
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
雷伟
依托单位:
学科分类:
心肌损伤、修复、重构和再生
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
雷伟
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中文摘要
心肌纤维化是各种心脏疾病的共同病理表现,也是心力衰竭的重要诱因;被公认为心衰防治的新靶标。长链非编码RNAs(lncRNAs)与心脏疾病的发生和发展有密切关系,在临床诊断和靶向治疗中极具应用前景。项目组高通量筛选发现lncRNA uc008ppm.1在纤维化组织中特异性表达,干涉uc008ppm.1后显著抑制体外成纤维细胞增殖和向肌成纤维细胞转化等,并改善心梗小鼠心功能;推测uc008ppm.1是抑制心肌纤维化,防治心衰的新靶点。本研究拟通过临床大样本分析和小鼠心梗模型明确uc008ppm.1作为心肌纤维化诊断标志及心衰防治靶点的潜能;基于高通量互作筛选、以uc008ppm.1/Sfrp2/HuR为核心,系统阐述uc008ppm.1调节心肌纤维化的多维协同调控机制。本研究将有助于解析lncRNAs调节心肌纤维化的分子机制,为以lncRNAs为靶点进行心血管疾病临床诊断和治疗提供新的思路。
英文摘要
As a hallmark of various heart diseases, cardiac fibrosis ultimately leads to end-stage heart failure. Anti-fibrosis is representing a potential therapeutic strategy for heart failure. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of heart disease, and hold great promise to serve as important biomarkers and therapeutic targets. Our preliminary studies found that: 1) lncRNA uc008ppm.1 is selectively expressed in the fibrotic tissue after myocardial infarction; 2) uc008ppm.1 shRNAs significantly inhibited proliferation of primary cultured fibroblasts and their transformation into myofibroblasts; 3) inhibition of uc008ppm.1 expression could obviously improve function of infarcted mouse heart. These data raised the possibility of using uc008ppm.1 as a target to prevent cardiac fibrosis and subsequent heart failure, which needs to be verified in our project. We will evaluate the clinical relevance of uc008ppm.1 in diagnostic assessments of cardiac fibrosis by analyzing its expression level in fibrotic heart tissues and blood samples from heart failure patients; investigate its function in different stages of cardiac fibrosis in infarcted mouse heart; illustrate its cellular and molecular mechanisms by high-throughput screening of uc008ppm.1 DNA/RNA/protein interactions; and further study the interactions among uc008ppm.1 and two fibrosis-related genes Sfrp2 and HuR, as well as the roles of these interactions in cardiac fibrosis. This study will be helpful for the further understanding of basic molecular mechanism underlying cardiac fibrosis, and provide new clues for developing effective diagnosis and/or treatment strategy for heart diseases.
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专利列表
DOI:10.3389/fcell.2021.672039
发表时间:2021
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Jiang X;Chen Y;Liu X;Ye L;Yu M;Shen Z;Lei W;Hu S
通讯作者:Hu S
DOI:10.1016/j.omtn.2023.04.020
发表时间:2023-06-13
期刊:MOLECULAR THERAPY NUCLEIC ACIDS
影响因子:--
作者:Ding, Fengyue;Wu, Hongchun;Han, Xinglong;Jiang, Xue;Xiao, Yang;Tu, Yuanyuan;Yu, Miao;Lei, Wei;Hu, Shijun
通讯作者:Hu, Shijun
DOI:10.1016/j.ecoenv.2023.114931
发表时间:2023-04
期刊:Ecotoxicology and environmental safety
影响因子:6.8
作者:Chenghong Long;Zhenru Li;Shijin Liang;Sitong Yao;Songqi Zhu;Lin Lu;Rui Cao;Yingni Chen;Yuxin Huang;Yongjiang Ma;Wei-Xiang Lei;Xiaohuan Liang
通讯作者:Chenghong Long;Zhenru Li;Shijin Liang;Sitong Yao;Songqi Zhu;Lin Lu;Rui Cao;Yingni Chen;Yuxin Huang;Yongjiang Ma;Wei-Xiang Lei;Xiaohuan Liang
Retinoic acid promotes metabolic maturation of human Embryonic Stem Cell-derived Cardiomyocytes
视黄酸促进人胚胎干细胞来源的心肌细胞的代谢成熟
DOI:10.7150/thno.44146
发表时间:2020-01-01
期刊:THERANOSTICS
影响因子:12.4
作者:Miao, Shumei;Zhao, Dandan;Hu, Shijun
通讯作者:Hu, Shijun
Generation of an EFNB2-2A-mCherry reporter human embryonic stem cell line using CRISPR/Cas9-mediated site-specific homologous recombination
使用 CRISPR/Cas9 介导的位点特异性同源重组生成 EFNB2-2A-mCherry 报告基因人胚胎干细胞系
DOI:10.1016/j.scr.2021.102241
发表时间:2021
期刊:Stem Cell Research
影响因子:1.2
作者:Ying Huang;Hongchun Wu;Xinglong Han;Jie Wu;Miao Yu;Zhen-ao Zhao;Zhenya Shen;Shijun Hu;Wei Lei
通讯作者:Wei Lei
miR-148a对iPSCs的心肌分化能力和心肌梗死治疗效果的调节机制研究
- 批准号:81600218
- 项目类别:青年科学基金项目
- 资助金额:17.5万元
- 批准年份:2016
- 负责人:雷伟
- 依托单位:
OX40/OX40L信号及其介导的CD4+OX40+T细胞活化在支气管哮喘发病机制中的实验研究
- 批准号:81300026
- 项目类别:青年科学基金项目
- 资助金额:23.0万元
- 批准年份:2013
- 负责人:雷伟
- 依托单位:
国内基金
海外基金
