作为一种新型机械敏感调节器的内皮炎症的RHOJ
WenQiang Liu1, Yue Zeng1, LiHan Huang1
1Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518033, Guangdong, PR China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), PR China.
Biochemical and biophysical research communications
|June 4, 2023
概括
高剪切应力 (HSS) 通过降低ras同源家族成员J (RHOJ) 的调节来减少内皮炎症. 在内皮细胞 (ECs) 中抑制RHOJ为内皮功能障碍提供了一种治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 生理学高剪压 (HSS) 对于维持内皮平衡和通过抑制炎症抑制动脉样硬化至关重要.
- 通过HSS对内皮细胞 (ECs) 施加抗炎作用的精确分子机制仍然不完全理解.
研究的目的:
- 阐明通过HSS调节内皮炎症的分子机制.
- 为了研究ras同类家族成员J (RHOJ) 在HSS介导的内皮稳定中的作用.
主要方法:
- 定量实时PCR和西部抹迹来评估RHOJ,VCAM-1和ICAM-1的表达.
- RNA测序以识别RHOJ向的基因和途径.
- 甲基化RNA免疫沉降测序 (MeRIP-seq) 探索N6-甲基氨酸 (m6A) 修饰的作用.
主要成果:
- 在EC中,HSS显著降低了RHOJ mRNA和蛋白质水平.
- 沉默RHOJ降低了促炎标志物 (VCAM-1,ICAM-1) 和单细胞粘附,而RHOJ过度表达具有相反的效果.
- RNA-seq确定了YAP1,HO1,MCP1和NF-κB等通路作为RHOJ的目标.
- 由HSS引起的RHOJ下调取决于m6A修改,涉及METTL3,YTHDF3和YTHDC1/2.2.
结论:
- 通过降低RHOJ表达的调节,HSS抑制内皮炎症并促进平衡.
- 在调节内皮质炎症反应方面,RHOJ起着至关重要的作用.
- 在EC中准RHOJ为治疗内皮功能障碍和动脉样硬化提供了潜在的治疗途径.
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