高酸盐诱导的JAK-STAT信号维持血管光滑肌细胞炎症并限制化
Federica Macrì1, Ilaria Vigorito1, Stefania Castiglione1
1Unit of Experimental Cardio-Oncology and Cardiovascular Aging, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy.
Biomolecules
|January 23, 2024
概括
血管化包括炎症. 阻断JAK-STAT通路减少了细胞和小鼠模型中的炎症和增加沉积,这表明了新的联系.
科学领域:
- 生物医学科学 生物医学科学
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
背景情况:
- 血管化 (VC) 是一种与年龄相关的疾病,涉及动脉中酸沉积.
- 血管光滑肌细胞 (VSMC) 的骨质变化驱动VC.
- 简氏酶信号转换器和转录激活器 (JAK-STAT) 途径与炎症有关.
研究的目的:
- 研究JAK-STAT信号通路在VSMC化中的作用.
- 探索炎症和血管化之间的关系.
主要方法:
- 人类大动脉光滑肌细胞 (HASMCs) 在高酸盐 (Pi) 中培养.
- 使用Alizarin染色和色度测试测量沉积量.
- 评估了JAK-STAT通路激活,炎症因子释放和基因表达. 在HASMC和小鼠大动脉环中使用JAK抑制剂I进行了JAK-STAT抑制.
主要成果:
- 在HASMC中Pi诱导的化导致IL-6,IL-8和MCP-1的释放,以及JAK1-JAK3和STAT1.1的激活.
- 在化小鼠主动脉中观察到-STAT1.
- 抑制JAK-STAT通路减少了HASMC的扩散和促炎性细胞因子的释放,但增加了沉积和RUNX2的表达,加剧了大动脉环化.
结论:
- 在VSMC化中,JAK-STAT通路起着重要作用.
- 阻止JAK-STAT级联是血管化的潜在治疗策略.
- 这些发现表明,VSMC炎症和血管化之间存在新的联系.
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