CD5L是转录因子 Nrf2 的标
Sharadha Dayalan Naidu1, Abel D Ang1, Charlotte Lim Jia Yee1
1Division of Cancer Research, School of Medicine, University of Dundee, Scotland, United Kingdom.
Biochemical and biophysical research communications
|June 22, 2025
概括
转录因子 Nrf2 调节 CD5L 的表达,CD5L 是一种与炎症和纤维化有关的蛋白质. 激活Nrf2可以提高CD5L水平,这可能是治疗肺纤维化的一种策略.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- CD5抗原样 (CD5L),也称为巨细胞表达的亡抑制剂 (AIM),是一种分泌的蛋白质,在炎症,感染和纤维化中起作用.
- CD5L的转录调节是复杂的,并未完全理解.
研究的目的:
- 研究转录因子NF-E2 p45相关因子2 (Nrf2) 在调节CD5L基因表达中的作用.
- 探索Nrf2激活剂在调节CD5L水平中的潜力,用于治疗应用,特别是肺纤维化.
主要方法:
- 骨髓衍生的巨细胞的蛋白质组分析,具有不同的Nrf2表达.
- 在小鼠和人类巨细胞中对Nrf2活性进行遗传和药理学操纵.
- 芯片测序分析以确定Cd5l促进体附近的Nrf2结合位点.
- 编辑CRISPR/Cas9基因以删除假定的Nrf2结合序列.
- 评估复合CD5L对肺纤维细胞中TGFβ诱导的纤维化反应的影响.
主要成果:
- Nrf2在巨细胞中直接控制CD5L基因表达.
- 增加的Nrf2活性与增加的CD5LmRNA和蛋白质水平相关.
- Nrf2与抗氧化剂反应元素 (ARE) 类似的序列结合,这些序列在Cd5l促进体的上游.
- 这些ARE类序列的删除显著降低了CD5L表达.
- 再组合的CD5L抑制了人类肺纤维细胞中TGFβ驱动的纤维化.
结论:
- Nrf2是通过特定的DNA结合基因对CD5L表达的关键调节者.
- 像奥马维洛克索隆这样的nrf2激活剂可能是增加CD5L水平和对抗肺纤维化的一种治疗方法.
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