iRHOM2通过CX3CL1调节炎症和内皮屏障的透性
Huiyuan Yan1, Junsong Wu2, Huilian Yan3
1Department of Internal Medicine, Children's Hospital of Fudan University, Shanghai 201102, P.R. China.
Experimental and therapeutic medicine
|June 5, 2023
概括
无活性的象牙状蛋白2 (iRHOM2) 调节急性肺损伤 (ALI) 的炎症和亡. 沉默iRHOM2可以防止LPS诱导的ALI,但CX3CL1过度表达会抵消这种保护作用.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 病理生理学 病理生理学
背景情况:
- 急性肺损伤 (ALI) 的特征是炎症和血管透性增加.
- 肺微血管内皮细胞 (HPMVEC) 是ALI发病的核心.
- 在ALI中,非活性状蛋白2 (iRHOM2) 的作用需要进一步阐明.
研究的目的:
- 调查iRHOM2在脂聚糖 (LPS) 诱导的ALI中的作用.
- 为了检查ALI中iRHOM2和C-X3-C动机化学激素连接体1 (CX3CL1) 之间的相互作用.
- 确定iRHOM2对内皮屏障功能和炎症的影响.
主要方法:
- 带有iRHOM2静音和CX3CL1过度表达的LPS诱导HPMVEC模型.
- 检测细胞活力 (CCK-8),炎症标志物 (TNFα,IL-1β,IL-6,p65),细胞亡 (TUNEL) 和内皮透性.
- 紧密结合蛋白的免疫光和西部涂抹 (ZO-1,VE-cadherin,occludin).
- 蛋白质相互作用分析的免疫共降.
主要成果:
- 在LPS治疗下,HPMVEC活力下降,炎症,亡和透性增加.
- 通过iRHOM2静音,可以逆转LPS引起的有害影响.
- 在LPS治疗的细胞中观察到CX3CL1上调.
- 过度表达CX3CL1抵消了iRHOM2沉默的保护作用.
结论:
- iRHOM2作为ALI的新型调节剂,影响炎症,细胞亡和内皮屏障完整性.
- iRHOM2和CX3CL1之间的相互作用在LPS诱导的ALI的发病过程中至关重要.
- 针对iRHOM2可能为ALI提供治疗潜力.
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