调节衰老的PNUTS通过SEMA3B抑制来维持内皮屏障功能
Noelia Lozano-Vidal1,2, Laura Stanicek1,2,3, Diewertje I Bink1,2
1Department of Physiology, Amsterdam UMC, VU University, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
酸酶1核向子单元 (PNUTS) 对内皮细胞健康至关重要. 失去PNUTS会加速内皮老化,导致器官衰竭,但向3B (SEMA3B) 可以恢复屏障功能.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 衰老的研究研究.
- 血管恒温是血管的恒温.
背景情况:
- 内皮衰老有助于与年龄有关的心血管疾病.
- 酸酶1核向子单元 (PNUTS) 与心肌细胞衰老有关.
- 在内皮细胞衰老中PNUTS的作用需要研究.
研究的目的:
- 阐明PNUTS在内皮细胞衰老和恒温的作用.
- 在内皮细胞中识别由PNUTS调节的下游通路.
- 探索与年龄相关的内皮功能障碍的潜在治疗点.
主要方法:
- 在人静脉内皮细胞 (HUVECs) 中 PNUTS 沉默.
- 产生和分析内皮特异性诱导性PNUTS缺陷小鼠 (PNUTSEC-KO).
- 沉默的HUVECs和小鼠肺组织的转录组分析 (RNA-seq).
- 评估内皮老化,血管生成,屏障功能和器官完整性.
主要成果:
- 在衰老的内皮细胞中,PNUTS的表达减少.
- 在体外和体内,PNUTS缺陷重现了内皮老化的特征,包括衰老和屏障功能障碍.
- 在小鼠中,PNUTS删除导致多器官衰竭和血管泄漏.
- 在PNUTS-PP1复合体调节3B (SEMA3B) 的表达.
- 在PNUTS损失后,SEMA3B敲除挽救了内皮屏障功能.
结论:
- PNUTS在维持内皮细胞平衡和预防过早衰老方面发挥着至关重要的作用.
- PNUTS-SEMA3B轴是内皮屏障完整性的关键调节器.
- 针对PNUTS-SEMA3B途径提供了一种潜在的策略,以打击与年龄相关的内皮功能障碍和血管疾病.
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