YAP/TAZ激活通过维持衰老的肺上皮细胞来调解PQ诱导的肺纤维化
Youjia Yu1, Chunyan Chu1,2, Kang Wang1
1Department of Forensic Medicine, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China.
Respiratory research
|May 18, 2024
概括
帕拉克瓦特中毒通过诱导肺上皮细胞衰老和Hippo-YAP/TAZ激活引起肺纤维化. 这一途径促进纤维化,为帕拉克瓦特诱导的肺损伤提供了新的治疗点.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 帕拉克瓦特 (PQ) 中毒是致死性肺纤维化的主要原因.
- PQ诱导的肺纤维化背后的机制,特别是上皮细胞衰老的作用,尚未完全理解.
研究的目的:
- 为了研究肺上皮细胞衰老和Hippo-YAP/TAZ通路在帕拉克瓦特诱导的肺纤维化中的作用.
- 为了探索帕拉克瓦特中毒的潜在治疗点.
主要方法:
- 使用了暴露于PQ的C57BL/6小鼠和人类上皮细胞.
- 分析了PQ诱导的肺上皮细胞衰老和Hippo-YAP/TAZ激活.
- 研究了Yap/Taz对纤维化和衰老标志物的影响.
- 研究了YAP/TAZ干扰对衰老细胞的亡的影响.
主要成果:
- 在小鼠和人类细胞中,PQ诱导了肺上皮细胞衰老和Hippo-YAP/TAZ激活.
- 衰老细胞分泌SASP因子,促进纤维细胞的转化.
- 雅普/塔兹 Knockdown 降低了益纤维菌标记物 (Ctgf) 和衰老标记物 (p16,p21),缓解了纤维化.
- 在衰老细胞中干扰YAP/TAZ降低了生存率并增加了亡.
结论:
- 肺上皮细胞衰老中的Hippo-YAP/TAZ激活是PQ诱导的肺纤维化的一个关键机制.
- 这一途径为管理PQ中毒和相关肺部疾病提供了新的治疗点.
- 维持细胞衰老和细胞亡之间的平衡对于肺部平衡至关重要.
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