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在脑损伤后,Wnt5a/Ror2促进星球细胞的Nrf2介导组织保护功能

Mitsuharu Endo¹, Yuki Tanaka¹, Mayo Fukuoka¹

¹Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe, Japan.

|October 31, 2023

概括

反应性星球细胞保护和修复脑损伤. 基本纤维细胞生长因子 (bFGF) 激活Wnt5a/Ror2信号传递,促进抗氧化反应,并在脑出血后促进血脑屏障的修复.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

星球细胞对于脑损伤的修复至关重要,但控制它们的保护功能的分子机制尚不清楚.
了解星球细胞信号通路对于开发治疗大脑损伤的治疗策略至关重要.

研究的目的:

阐明了在脑损伤后调节反应性天体细胞功能的分子机制.
调查基本纤维细胞生长因子 (bFGF) 和Wnt5a/Ror2信号传导在星体介导组织保护和修复中的作用.

主要方法:

利用刺伤 (SW) 脑损伤和原酶诱导的脑内出血 (ICH) 的小鼠模型.
在培养的天体细胞中分析了基因表达和蛋白质信号.
研究了bFGF,炎症性细胞因子和Wnt5a/Ror2激活对天体细胞功能的影响.
评估了增强Wnt5a/Ror2信号对细胞损伤和血脑屏障修复的影响.

主要成果:

在受伤的小鼠大脑中观察到bFGF上调.
bFGF与炎症性细胞因子协同作用,激活星球细胞中E2F1-介导的Ror2转录.
Wnt5a/Ror2信号激活导致了Nrf2核积累和抗氧化基因的增加表达 (例如,血红氧酶1).
增强的Wnt5a/Ror2信号传递减少了半膜诱导的细胞损伤,并促进了血脑屏障的修复.

结论:

由bFGF启动的Wnt5a/Ror2信号通路调节了脑损伤后天体细胞的保护功能.
这一途径增强了抗氧化剂防御,并促进了血脑屏障的修复,提供了潜在的治疗点.

关键词:

Nrf2 没有任何问题.在Ror2上,它是Ror2.没有Wnt5a.bFGFF的bFGFF的bFGF是什么意思脑损伤是因为脑损伤.氧化应激是一种氧化应激.反应性星球细胞的反应性星球细胞.

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