河马协作激活剂TAZ加剧了西斯普拉丁诱导的急性损伤
Xian Xue1, Xingwen Zhu2, Lu Zhou2
1Center for Kidney Disease, The 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Kidney diseases (Basel, Switzerland)
|December 12, 2024
概括
具有PDZ结合动机 (TAZ) 的转录协活性剂通过促进铁亡,加剧急性损伤 (AKI). 抑制TAZ-PPARδ相互作用可以保护脏免受西斯胺诱导的损伤,这表明TAZ是AKI的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 脏生理学 脏生理学
- 分子医学是分子医学.
背景情况:
- 河马信号通路效应体,具有PDZ结合动机 (TAZ) 的转录协活性体,对于细胞平衡至关重要.
- 在管状细胞存活中TAZ的特定作用及其在急性损伤 (AKI) 中的参与尚未得到充分理解.
研究的目的:
- 调查TAZ在西斯普拉丁诱导的AKI中的作用.
- 阐明TAZ影响管状细胞铁和损伤的分子机制.
主要方法:
- 通过RNA-seq,西部斑块和免疫组织化学,检查了cisplatin诱导的AKI脏中的TAZ表达.
- 产生的管状特异性TAZ淘汰赛小鼠,以评估其功能在毒性.
- 利用免疫沉质谱法来识别相互作用的蛋白质.
主要成果:
- 在注射西斯后,在管状细胞中观察到TAZ激活.
- 管状细胞中TAZ的条件删除赋予了对铁亡的耐药性,并对AKI进行了保护.
- TAZ过度表达加剧了西斯普拉丁诱导的铁亡,机械地通过减少以PPARδ-依赖的方式减少谷氨过氧化酶4 (GPX4) 表达.
结论:
- 齐斯普拉丁诱导的AKI和管状细胞铁死是由TAZ-PPARδ相互作用通过GPX4调节调节的.
- TAZ成为缓解AKI和铁亡的潜在治疗标.
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