一个调节循环涉及细胞染色体P450可溶性环氧化酶轴和TGF-β信号传递
Xiaoming Li1, Sebastian Kempf1, Fredy Delgado Lagos1
1Goethe University, Institute for Vascular Signalling, Centre for Molecular Medicine, Frankfurt am Main, Germany.
iScience
|October 14, 2024
概括
溶性环氧化酶 (sEH) 通过控制脂肪酸代谢产物来调节炎症. 这项研究揭示了sEH对于巨细胞再极化和功能至关重要,由TGF-β信号传递介导.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 脂肪酸代谢物,包括由细胞P450酶和可溶性环氧化酶 (sEH) 产生的代谢物,在调节炎症过程中起着至关重要的作用.
- 转化生长因子β (TGF-β) 是一种关键的细胞因子,参与免疫细胞的分化和功能.
研究的目的:
- 研究可溶性环氧化酶 (sEH) 在TGF-β诱导的巨细胞极化中的作用.
- 阐明sEH影响巨细胞表型和功能的分子机制.
主要方法:
- 巨细胞培养和操纵sEH表达/活动.
- 对基因表达特征和蛋白质信号通路 (例如,Alk5,Smad2,Smurf2) 的分析.
- 代谢分析以确定改变的脂肪酸代谢产物.
主要成果:
- 由TGF-β诱导的巨细胞两极化转化为亲溶解的表型,需要Alk5和Smad2的激活,从而增加sEH的表达和活性.
- 缺少sEH的巨细胞表现出受损的复极化,减少的细胞化和持续的促炎性基因表达.
- 11,12-Epoxyeicosatrienoic acid (EET),是sEH缺陷巨细胞中的一种改变的代谢物,通过减少Alk5表达通过Smurf2转位来模仿sEH删除的效果并抑制TGF-β信号传递.
- sEH活动会代谢11,12-EET,从而促进TGF-β信号传递,并防止Alk5降解.
结论:
- sEH的表达是由巨细胞中的TGF-β信号调节的.
- 涉及sEH,11,12-EET和TGF-β1的自克林循环对于调节巨细胞功能和炎症解决至关重要.
- 针对sEH/11,12-EET通路可能为炎症性疾病提供治疗策略.
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