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鉴定与铁亡相关的基因在由横向大动脉收缩引起的心力衰竭中
Jian Jun Gu1,2, Tian Jian Du1,2, Li Na Zhang3
1Department of Cardiology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China.
Journal of inflammation research
|November 6, 2023
概括
这项研究确定了与铁亡相关的关键基因 (Mapk14,Hif1a,Ddit3,Tlr4,Ptgs2) 参与心力衰竭 (HF). 这些基因可以通过调节铁灭症来作为治疗HF的潜在治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 生物医学数据科学 生物医学数据科学
背景情况:
- 心力衰竭 (HF) 是一个重要的全球健康问题,与心室功能障碍和高死亡率有关.
- 铁,一种由铁依赖性脂质过氧化驱动的受调细胞死亡形式,越来越多地被认为是其在HF病原发生中的作用.
研究的目的:
- 识别和验证与铁亡相关的新型基因 (FRG) 作为潜在的生物标志物和心力衰竭的治疗点.
- 通过综合生物信息学和实验方法,探索HF背景下铁化背后的分子机制.
主要方法:
- 从HF的小鼠横向大动脉收缩 (TAC) 模型中利用基因表达特征 (GSE36074).
- 从FerrDb数据库中整合数据以识别FRG,并使用GEO2R进行差异基因表达分析.
- 进行重叠分析以找到与铁灭相关的差异表达基因 (FRDEG),然后进行聚类,功能丰富 (GO,KEGG) 和蛋白质与蛋白质相互作用 (PPI) 网络分析.
- 构建了转录因子 (TF) -FRDEG和微RNA (miRNA) -FRDEG网络,并使用定量逆转录PCR (RT-qPCR) 和免疫组织化学 (IHC) 验证了关键FRDEG.
主要成果:
- 在TAC诱导的HF模型中,在1918个DEG中确定了59个显著差异表达的FRG.
- 功能丰富分析表明FRDEG与亡调节,FoxO信号传递,VEGF信号传递,亡和铁亡有关.
- 通过PPI网络确定了五种关键FRDEG (Mapk14,Hif1a,Ddit3,Tlr4,Ptgs2),并在mRNA和蛋白质水平上进行实验验证.
结论:
- 已确定Mapk14,Hif1a,Ddit3,Tlr4和Ptgs2是关键的与铁化相关的基因,可能与HF发育有关.
- 这些已识别的基因代表了心力衰竭的有前途的治疗标,通过调节铁亡途径为治疗提供了新的途径.
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