内皮H2S-AMPK功能障碍调高了血管新生素PAI-1因子,并导致肺纤维化
Xiangqi Chen1, Han Wang1, Chuan Wu1
1Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, NHC Key Laboratory of Chronobiology, Development and Related Diseases of Women and Children, Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Redox biology
|January 24, 2024
概括
硫化 (H2S) -AMP激活蛋白激酶 (AMPK) 途径感知纤维化应激,在肺纤维化中调节可塑性原激活剂抑制剂-1 (PAI-1). 恢复H2S和激活AMPK可以缓解纤维化.
科学领域:
- 血管生物学 血管生物学
- 代谢途径 代谢途径
- 器官纤维化 器官纤维化
背景情况:
- 血管血管神经系统功能障碍有助于器官纤维化.
- 衰老和代谢障碍破坏了这个系统.
- 感知纤维化风险的机制仍然不清楚.
研究的目的:
- 在血管血管系统中识别纤维化应激的传感器.
- 阐明了将代谢途径与肺纤维化联系起来的机制.
- 研究硫化 (H2S) 和AMP激活蛋白激酶 (AMPK) 的作用.
主要方法:
- 对人类和小鼠纤维化肺部数据的分析.
- 研究了内皮细胞中的H2S-AMPK通路.
- 用于AMPK激活的甲福林和用于PAI-1抑制的提普拉克斯林.
- 评估肺功能和纤维化特征.
主要成果:
- 内皮AMPK失活与肺纤维化严重程度和肺功能减弱相关.
- AMPK无活化激活了YAP和PAI-1,在小鼠中加剧了纤维化.
- 由于H2S缺乏,AMPK被禁用,YAP-PAI-1被激活.
- 甲胺和提普拉克斯林,以及H2S补充剂,缓解了肺纤维化.
结论:
- H2S-AMPK通路在内皮细胞中充当纤维化应激传感器.
- 这一途径调节PAI-1的表达,并有助于肺纤维化发展.
- 针对H2S-AMPK信号提供了一个潜在的治疗策略,用于肺纤维化.
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