卡塞普辛L通过BMPR2/GSDME介导的热致死促进肺高血压
Zhouyangfan Peng1,2, Xue-Yang Luo3, Xinyi Li3
1The Center for Vascular Disease and Translational Medicine, the Third Xiangya Hospital (Z.P., Yapei Li., Y.W., B.P., Z.Z., C.Q., Xiaohui Li, A.F.C.), Central South University, Changsha, China.
卡瑟普辛L通过降解BMPR2促进肺高血压 (PH),导致称为热亡的编程细胞死亡. 降低甲素L水平可以帮助治疗PH并恢复内皮功能.
科学领域:
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 肺高血压 (PH) 是一种严重的疾病,涉及肺血管重塑和内皮损伤.
- lysosomal 蛋白酶 cathepsin L 在细胞过程中发挥作用,其失调与PH有关.
- 骨形态遗传蛋白II型受体 (BMPR2) 缺乏是已知的PH的原因,与细胞死亡途径有关.
研究的目的:
- 为了研究 cathepsin L 在 PH 病变发生过程中的作用.
- 探索卡塞普辛L,BMPR2和PH中的火死之间的潜在联系.
- 为了确定是否向cathepsin L可能是PH的治疗策略.
主要方法:
- 在人类PH样本和动物模型中评估了cathepsin L表达.
- 使用体内模型来评估甲素L对PH进展和血管重塑的影响.
- 采用了分子技术 (siRNA,抑制剂,晶体病毒) 来研究肺动脉内皮细胞中甲素L的机制.
主要成果:
- 在PH患者和模型中观察到升高的cathepsin L表达.
- 基因去除甲素L改善了大鼠的PH指标,包括减少血管重塑和恢复内皮完整性.
- 发现 cathepsin L 通过降解 BMPR2 来诱导 pyroptosis,从而抑制 BMPR2 信号传递.
结论:
- 甲素L通过降解BMPR2来驱动PH的发展,这会触发-3/气体皮质素E (GSDME) 介导的内皮质质灭症.
- 恢复 BMPR2 信号传输可以抵消 cathepsin L. 的 pro-pyroptotic 作用.
- 这些发现突出了cathepsin L作为PH的关键调解者和潜在的治疗点.
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