通过针对PTPN4与miR-134-5pp,CircDLGAP4诱导自并改善动脉样硬化中的内皮细胞功能障碍
Yan Xiong1, Hui Huang2, Fuli Chen1
1Department of Cardiology and Cardiovascular Disease Research Institute, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Environmental toxicology
|August 24, 2023
概括
循环RNA circDLGAP4通过促进细胞健康和减少炎症,显示出对动脉样硬化 (AS) 的保护作用. 这项研究揭示了它在circDLGAP4/miR-134-5p/PTPN4通路中的调节作用,为AS提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
- 在RNA生物学,RNA生物学.
背景情况:
- 循环RNAs (circRNAs) 越来越多地被认为是它们在各种疾病中的作用,包括动脉样硬化 (AS).
- 已经确定了circDLGAP4,一种新的circRNA,其表达在AS病变发生过程中发生了变化.
研究的目的:
- 研究circDLGAP4在动脉样硬化中的作用和机制.
- 在AS的背景下,阐明监管轴 circDLGAP4/miR-134-5p/PTPN4.
主要方法:
- 动脉样硬化模型是使用人类静脉内皮细胞 (HUVECs) 中的氧化低密度脂蛋白 (ox-LDL) 和小鼠模型中的高脂肪饮食来建立的.
- 进行了功能性测试,以评估circDLGAP4对细胞增殖,自,细胞亡和炎症的 in vitro 和 in vivo 影响.
- 进行了机制测试,以探索circDLGAP4,miR-134-5p和PTPN4.4之间的相互作用.
主要成果:
- CircDLGAP4通过促进增殖和自,同时抑制ox-LDL治疗的HUVEC中的亡和炎症,从而改善内皮屏障功能,证明了保护作用.
- 循环DLGAP4直接针对miR-134-5p,这反过来又调节了PTPN4. 敲除PTPN4可以逆转circDLGAP4或miR-134-5p操纵的影响.
- 在体内研究表明,减少circDLGAP4或增加miR-134-5p加剧了AS表型,包括增加斑块面积,减少自和升高的炎症细胞因子.
结论:
- CircDLGAP4通过调节自和改善内皮功能障碍,在AS中发挥着关键的保护作用.
- 圆DLGAP4/miR-134-5p/PTPN4轴代表了与AS发展和进展有关的重要途径.
- 这个轴为治疗动脉样硬化提供了潜在的治疗点.
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