埃克1/2-EGR1信号通路参与了小鼠巨细胞中脂聚糖诱导的转化生长因子-β1表达
Weimin Zhao1, Hong Wang2, Chaohui Dai1
1Jiangsu Province Engineering Research Center of Precision Animal Breeding, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, China.
Microbial pathogenesis
|March 8, 2025
概括
脂多糖 (LPS) 通过Erk1/2-EGR1通路在巨细胞中增强TGF-β1. 这项研究揭示了一种与以前已知的途径截然不同的新机制,增强了我们对免疫反应的理解.
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:
- 已知脂聚糖 (LPS) 能刺激转化生长因子β1 (TGF-β1) 的表达.
- 虽然NF-κB/METTL3/METTL14和AMPK通路有关,但在小鼠巨细胞中,精确的调节机制尚不清楚.
研究的目的:
- 阐明LPS调节小鼠巨细胞TGF-β1表达的分子机制.
- 确定参与LPS诱导的TGF-β1表达的关键信号通路和转录因子.
主要方法:
- 使用RAW264.7小鼠巨细胞系的体外研究.
- 在LPS挑战后对TGF-β1mRNA和蛋白质水平的分析.
- 对MAPK (p38,Erk1/2,JNK) 和NF-κB通路激活的研究.
- 评估早期生长反应1 (EGR1) 的水平和功能.
- 双 luciferase 报告器和染色体免疫沉-PCR (ChIP-PCR) 试验.
主要成果:
- 在mRNA和蛋白质水平上,LPS显著增加了TGF-β1的表达.
- Erk1/2通路的激活至关重要,因为它的阻断完全取消了LPS诱导的TGF-β1表达.
- 在LPS治疗中,EGR1水平升高,EGR1是Erk1/2.2的下游调节剂.
- 抑制EGR1显著降低了LPS诱导的TGF-β1表达.
- 证实EGR1是关键的转录因子,与TGF-β1促进体结合.
结论:
- LPS主要通过Erk1/2-EGR1信号通路调节小鼠巨细胞中的TGF-β1表达.
- 这种Erk1/2-EGR1通路代表了LPS诱导的TGF-β1表达的新机制,与以前识别的通路不同.
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