循环甲肝素D通过促进中性粒细胞透到大脑中来加剧受伤引起的脑损伤
Yu Liang1, Dan Zhao1,2, Peng-Fei Wu2
1Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education China Medical University Shenyang China.
Journal of the American Heart Association
|October 28, 2025
概括
高水平的循环cathepsin D (CTSD) 通过激活内皮和增加中性粒细胞透,加剧脑损伤. 降低CTSD水平可以保护大脑免受损伤,并改善运动功能的恢复.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 血管内皮和白细胞通信调节大脑炎症.
- 血甲素D (CTSD) 的升高与血管事件有关.
- 循环中CTSD对内皮功能的影响尚不清楚.
研究的目的:
- 为了调查循环CTSD在脑损伤中的作用.
- 为了确定CTSD是否影响内皮细胞激活和白细胞透.
- 评估降低CTSD水平的治疗潜力.
主要方法:
- 使用高 (hCTSD) 或低 (CTSD) 循环CTSD水平的转基因小鼠.
- 接受创伤性和缺血性脑损伤的小鼠.
- 进行单细胞RNA测序以分析大脑基因表达.
- 通过VCAM-1研究了CTSD诱导的内皮激活的机制.
主要成果:
- hCTSDhi小鼠在脑损伤后表现出增加的中性粒细胞透和恶化的运动缺陷.
- 循环的CTSD功能作为非酶的亲CTSD,激活大脑内皮.
- 亲-CTSD调节VCAM-1表达,促进中性粒细胞的转移.
- 基因减少CTSD减弱了受伤引起的中性粒细胞透和运动缺陷.
结论:
- 循环的原型CTSD加剧了受伤后的脑损伤.
- 通过对内皮细胞VCAM-1进行上调调节,CTSD促进了中性粒细胞的透.
- 降低CTSD水平为脑损伤提供了一个潜在的治疗策略.
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