通过METTL3-介导的m6A修饰来稳定TRPM4mRNA,促进了状大动脉炎的炎症
Jianguo Wu1, Haozong Huang1, Wenkai Yang1
1Department of Cardiac and Macrovascular Surgery, Central People's Hospital of Zhanjiang, Guangdong province, China.
Heliyon
|June 13, 2024
概括
暂时受体潜力梅拉斯塔丁4 (TRPM4) 通过激活JNK-MAPK通路,驱动动脉疾病 (CAVD) 的炎症. 通过METTL3介导的TRPM4的m6A修饰提高了TRPM4的表达,为CAVD炎症提供了潜在的治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 暂时受体潜力梅拉斯4 (TRPM4) 通过平衡来调节免疫反应.
- TRPM4在形大动脉膜疾病 (CAVD) 炎症中的特定作用尚不清楚.
研究的目的:
- 研究TRPM4在CAVD中的表达和功能.
- 阐明TRPM4在CAVD炎症中的作用背后的分子机制.
主要方法:
- 定量实时PCR (qRT-PCR) 和西班牙血栓测量TRPM4mRNA和蛋白质水平.
- RNA下拉,RNA免疫沉降和双路西法酶记者试验以确定TRPM4相互作用和m6A修饰.
- TRPM4的淘汰,以评估其对炎症性细胞因子产生的影响.
主要成果:
- TRPM4,TLR4,IL-6,MCP-1,TNF-α和NF-κB p65的mRNA和蛋白质水平在化的大动脉膜组织中升高.
- TRPM4表达与炎症标志物呈正相关性,并通过METTL3介导的N6-甲基氨酸 (m6A) 修饰进行上调.
- 通过JNK-MAPK通路激活,TRPM4促进炎症;TRPM4敲击抑制了促炎性细胞因子的产生.
结论:
- 通过促进炎症,TRPM4在CAVD病变发生过程中发挥着关键作用.
- 通过JNK-MAPK信号通路,TRPM4的METTL3介导的m6A修饰有助于通过CAVD炎症.
- 准TRPM4为缓解CAVD炎症提供了一个潜在的治疗策略.
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