白血病抑制因子的增强效应揭示了TYK2信号在血管化中的关键作用
Ioana Alesutan1, Mehdi Razazian1, Trang T D Luong1
1Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Linz, Austria.
Kidney international
|July 31, 2024
概括
白血病抑制因子 (LIF) 通过激活TYK2信号来促进慢性病 (CKD) 的血管化. 抑制TYK2可能会减少CKD患者的血管化.
科学领域:
- 心血管生物学 心血管生物学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子医学是分子医学.
背景情况:
- 慢性病 (CKD) 中的中间血管化与炎症和高酸血症有关.
- 干白素6家族成员,包括白血病抑制因子 (LIF),都与血管化有关.
- 血管光滑肌细胞 (VSMC) 化是CKD的一个重要并发症.
研究的目的:
- 调查LIF在VSMC化中的作用.
- 阐明LIF介导的血管化所涉及的信号通路.
- 评估TYK2作为CKD中血管化的潜在治疗标.
主要方法:
- 在暴露于酸盐的VSMC中评估LIF表达.
- 研究了LIF,LIF受体 (LIFR) 和可溶性LIFR对VSMC化的影响.
- 研究了TYK2和STAT3信号通路的作用.
- 使用deucravacitinib可以抑制TYK2.
- 评估TYK2抑制和缺陷在ex vivo小鼠大动脉环和血管化的in vivo小鼠模型中.
主要成果:
- 在酸盐暴露后,VSMC中LIF表达增加.
- LIF补充剂加剧了VSMC化,而LIFR抑制改善了它.
- LIF诱导了TYK2和STAT3酸化;TYK2抑制削弱了LIF和酸盐效应.
- 在包括CKD模型在内的各种小鼠模型中,TYK2抑制和缺乏减少了血管化.
- 溶性LIFR显示对LIF具有对抗作用,减少VSMC化.
结论:
- 在CKD相关的血管化中,LIF起着重要作用.
- TYK2信号传递是LIF诱导和酸盐诱导血管化的中心调解者.
- 准TYK2代表了一种潜在的治疗策略,以减轻CKD中的血管化.
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