顺酸通过顺酸/SUCNR1轴加剧肺纤维化
Rishi Rajesh1,2, Agnes Anna Mooslechner1,2, Hannah Schweighofer1,2
1Division of Pharmacology, Otto Loewi Research Center, Lung Research Cluster, Medical University of Graz, Graz, Austria.
概括
顺酸及其受体SUCNR1通过促进纤维细胞激活来驱动肺纤维化. 准这种途径为异常性肺纤维化 (IPF) 提供了潜在的新疗法.
科学领域:
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
- 代谢学 代谢学 代谢学
背景情况:
- 异形性肺纤维化 (IPF) 是一种进展性肺病,其特征是膜破坏和纤维化.
- 在IPF患者中观察到变化的代谢物水平,包括糖酸盐.
- 纤维细胞在IPF的发病过程中发挥着核心作用.
研究的目的:
- 为了研究酸盐及其受体,酸盐受体1 (SUCNR1) 在肺纤维化中的作用.
- 为了确定酸盐对纤维细胞行为的影响和纤维细胞标记物表达.
- 评估向苏酸盐/SUCNR1轴的治疗潜力.
主要方法:
- 使用西方斑点,qPCR和局部杂交的SUCNR1表达分析.
- 使用IPF和正常的人类肺纤维细胞 (NHLF) 进行体外研究.
- 在活体研究中,使用白胺诱导的肺纤维化小鼠模型.
主要成果:
- SUCNR1在包括纤维细胞在内的各种肺细胞中表达.
- 酸盐治疗增加了纤维化标志物 (例如,阿尔法平滑肌动蛋白,原蛋白) 和IPF纤维细胞中的纤维细胞到肌纤维细胞过渡.
- 在体内, Succinate 加剧了小鼠的肺原积累和体重减轻.
- 抑制SUCNR1或抑制ERK取消了酸盐诱导的益菌效应.
结论:
- 顺酸和SUCNR1信号传递促进了肺纤维细胞在体外和体内都发生的益菌变化.
- 苏酸盐/SUCNR1轴代表了IPF治疗的潜在治疗标.
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