脂肪细胞调节纤维细胞功能,它们的损失有助于炎症性疾病中的纤维细胞功能障碍
bioRxiv : the preprint server for biology
|June 9, 2023
概括
健康的突纤维细胞依赖脂肪细胞衍生的皮质醇进行脂质代谢和恒温. 这种关键的信号在疾病中丢失,突出了关节疾病的新治疗点.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 突纤维细胞维持关节平衡,但可以驱动疾病状态的病理.
- 对于健康的突纤维细胞功能调节的理解仍然不充分.
研究的目的:
- 阐明调节健康的突纤维细胞功能的分子机制.
- 为了确定关键的信号通路和细胞类型,参与维护突平衡.
主要方法:
- 健康的人类突组织的RNA测序.
- 使用脂肪调节介质进行细胞培养实验.
- 在细胞模型中进行质谱和基因操纵 (NR3C1删除).
- 在体内研究涉及小鼠的突脂肪细胞枯竭.
主要成果:
- 健康的突纤维细胞表现出富含脂肪酸代谢和脂质运输的基因表达程序.
- 皮质醇被确定为健康纤维细胞表型的关键调节剂.
- 脂肪细胞通过Hsd11β1.1.通过synovium被确定为重要的皮质醇生产者.
- 皮质醇信号保护免受TNFα和TGFβ诱导的矩阵重塑,而这些细胞因子抑制皮质醇信号和脂肪生成.
结论:
- 脂肪细胞和皮质醇信号传递对于保持健康的突纤维细胞状态至关重要.
- 疾病状态涉及这种保护信号的丧失,细胞因子抑制皮质醇信号和脂肪生成.
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