RNA甲基化和转录组分析揭示了与诱导的肝损伤相关的关键调节途径
Hao Huang1, Guoliang Li2, Sihui Guo1
1School of Public Health, Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou 510515, China.
Chemical research in toxicology
|March 26, 2025
概括
暴露会通过改变m6A甲基化来损害肝脏. 在这种引起的肝损伤中,METTL14和CCR2是关键参与者,提供了潜在的治疗点.
科学领域:
- 表观遗传学和分子毒理学
- 肝脏疾病的发病因子 肝脏疾病的发病因子
背景情况:
- (Cd) 是一种有毒的环境污染物,已知会损害肝功能.
- 在Cd诱导的肝损伤中,表观遗传机制,特别是N6-甲基氨酸 (m6A) 甲基化,尚不清楚.
- 研究m6A甲基化的作用对于理解和治疗Cd相关的肝损伤至关重要.
研究的目的:
- 为了阐明m6A甲基化在引起的肝损伤中的作用.
- 为了确定关键的基因和途径参与表观遗传对暴露在肝脏的反应.
- 探索引起的肝损伤的潜在治疗标.
主要方法:
- 建立了化 (CdCl2) 诱导的肝损伤的小鼠模型.
- 利用甲基化RNA免疫沉降测序 (MeRIP-seq) 和RNA测序 (RNA-Seq) 来分析m6A概况和基因表达.
- 进行生物信息学分析以识别不同的甲基化和表达基因,重点关注丰富的信号通路.
主要成果:
- 暴露于CdCl2显著降低了m6A在肝脏中的甲基化水平.
- 确定了8355个独特的m6A峰值和1101个m6A修饰基因,其中673个显示差异甲基化.
- 联合分析显示,AGE-RAGE和PI3K-Akt信号通路的丰富,突出ITgax和CCR2作为关键基因. 观察到METTL14表达升高,其抑制通过m6A依赖的CCR2调节来调节Cd诱导的肝炎.
结论:
- m6A甲基化在引起的肝损伤中起着关键作用.
- METTL14及其下游标CCR2是肝炎和反应损伤的关键媒介.
- 这些发现为肝病的表观遗传机制提供了新的见解,并建议METTL14和CCR2作为潜在的诊断和治疗点.
更多相关视频
07:50Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
8.9K
07:16Rapid and Efficient Spatiotemporal Monitoring of Normal and Aberrant Cytosine Methylation within Intact Zebrafish Embryos
Published on: August 18, 2022
1.3K
相关概念视频
01:37Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
01:17Phase II Reactions: Methylation Reactions
104
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
104