核受体Nurr1调节了人类前炎性巨细胞中PPARγ的表达和活性
Eduardo Santana-Cisneros1, Miguel A Solís-Barbosa1, Norma C Segovia-Gamboa1
1Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico City, Mexico.
Scandinavian journal of immunology
|October 24, 2025
概括
核受体Nurr1通过稳定其蛋白质水平并减少压制性酸化,增强巨细胞中氧酶增殖器激活受体 (PPAR) 活性. 这揭示了Nurr1在调节炎症和其他PPARγ介导通路中的新机制.
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:
- Nurr1 (NR4A核受体家族) 通常通过NF-κB通路抑制炎症.
- Nurr1与氧酶增殖器激活受体 (PPAR) 相互作用,但它们在巨细胞中的功能关系尚不清楚.
研究的目的:
- 研究Nurr1在调节人体巨细胞内PPARγ活性中的作用.
主要方法:
- 人体单细胞分化为促炎性 (GM-MDMs) 和抗炎性 (M-MDMs) 巨细胞.
- 在不同的激活条件下评估Nurr1和PPARγ的蛋白质水平.
- 使用Nurr1 (C-DIM12) 和PPARγ (罗斯格利塔) 的激动剂来评估功能相互作用和对基因表达的下游影响 (CD36,PLIN2).
主要成果:
- 在GM-MDM中,Nurr1和PPARγ蛋白水平更高,并且具有正相关性.
- 通过C-DIM12激活Nurr1,通过稳定增加了PPARγ蛋白水平,并在Ser84.4降低了PPARγ酸化.
- 激活Nurr1增强了PPARγ向基因 (CD36,PLIN2) 的表达,并表现出抗炎作用.
结论:
- Nurr1通过稳定其蛋白质并降低抑制酸化来增强PPARγ转录活性.
- 这项研究揭示了Nurr1在巨细胞中调节炎症和其他PPARγ依赖途径的新机制.
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