通过m6AmRNA甲基化介导的MAPK信号调节了过敏性鼻炎中的鼻腔粘膜炎症反应
Ruikun Wang1,2, Jieqiong Liang1, Qian Wang3
1Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
Frontiers in immunology
|July 16, 2024
概括
N6-甲基氨酸 (m6A) 失调,特别是涉及ALKBH5,通过MAPK通路导致过敏性鼻炎 (AR) 的鼻炎. ALKBH5可以作为AR治疗的潜在生物标志物.
科学领域:
- 调查了表观遗传修饰在过敏性鼻炎的发病过程中的作用.
- 专注于N6-甲基氨酸 (m6A) mRNA修饰及其对炎症反应的影响.
背景情况:
- 过敏性鼻炎 (AR) 的发病过程涉及复杂的基因环境相互作用.
- 包括m6A在内的表观遗传修饰调节基因表达,但它们在AR中的作用尚不清楚.
研究的目的:
- 阐明m6A修饰在过敏性鼻炎和相关炎症反应中的功能.
- 确定特定的分子通路和涉及AR的表观遗传调节者.
主要方法:
- 使用卵和氧化建立了过敏鼻炎小鼠模型.
- 进行了组合的m6A和RNA测序,以分析m6A配置文件.
- 利用RT-qPCR和MeRIP-qPCR验证差异mRNA甲基化和m6A水平;抑制了Alkbh5的表达.
主要成果:
- m6A修饰在MAPK信号通路内的基因中得到了丰富,包括Map3k8,Erk2和Nfκb1.1.
- 在AR模型小鼠的鼻腔粘膜中,m6A擦拭剂Alkbh5的表达很高.
- Knockdown 的 Alkbh5 导致了增加的 MAPK 途径活动和显著的鼻子炎症.
结论:
- ALKBH5-介导的m6A失调有助于通过AR中的MAPK信号通路导致鼻膜炎症.
- ALKBH5成为过敏性鼻炎的潜在治疗生物标志物.
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