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PATJ调节细胞应激反应和中风后血管重塑
Mengqi Zhang1, Wei I Jiang2, Kajsa Arkelius1
1Department of Neurology, University of California- San Francisco, San Francisco CA, 94158, USA.
PALS1关联紧结结 (PATJ) 蛋白对细胞功能至关重要,可能有助于缺血性中风后的恢复. 这项研究揭示了PATJ.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 帕尔斯1关联紧结结 (PATJ) 蛋白与代谢疾病和中风有关.
- 它在代谢疾病和缺血性中风恢复中的确切作用尚不清楚.
- 已知PATJ参与细胞极化.
研究的目的:
- 在体外和体内研究PATJ的功能.
- 探索PATJ在与中风恢复相关的细胞过程中的作用.
- 了解PATJ在Yes相关蛋白 (YAP) -1信号通路中的参与.
主要方法:
- 使用CRISPR-Cas9产生PATJ淘汰 (KO) HEK293细胞.
- 使用RNA测序用于PATJKO细胞的转录分析.
- 在体内研究中使用了缺血性中风和C. elegans的小鼠模型.
- 在C. elegans的低氧条件下研究了PATJ同源 (mpz-1) 功能.
主要成果:
- 在小鼠中,经过缺血性中风后的内皮细胞中PATJ表达增加.
- PATJ KO细胞表现出改变的增殖,迁移,线粒体应激反应和YAP1信号传递.
- 在PATJ KO细胞中的转录重编程影响了血管发育,应激反应和新陈代谢中的基因.
- C. elegans PATJ同源 (mpz-1) 敲除会加剧神经元缺陷和缺氧下的死亡率.
结论:
- PATJ在细胞功能中发挥着重要作用,包括增殖,迁移和应激反应.
- PATJ对于维持神经元的完整性和生存至关重要,特别是在低氧压力下.
- 这些发现凸显了PATJ作为中风康复和神经血管修复的潜在治疗点.
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