上睑下垂
坏死性下垂
肾
急性肾损伤
发病机制
医学
程序性细胞死亡
癌症研究
肾缺血
细胞凋亡
肾脏疾病
炎症
坏死
化学
细胞生物学
缺血
急性肾小管坏死
氧化应激
活性氧
药理学
GPX4
病理
下调和上调
再灌注损伤
生物
免疫学
炎症体
内科学
生物化学
作者
Zhi Zhao,Jianzhong Wu,Huzi Xu,Cheng Zhou,Bicui Han,Han Zhu,Zhizhi Hu,Zhimei Ma,Zhang-Yin Ming,Ying Yao,Rui Zeng,Gang Xu
标识
DOI:10.1038/s41419-020-02871-6
摘要
Abstract Regulated necrosis has been reported to exert an important role in the pathogenesis of various diseases, including renal ischemia-reperfusion (I/R) injury. Damage to renal tubular epithelial cells and subsequent cell death initiate the progression of acute kidney injury (AKI) and subsequent chronic kidney disease (CKD). We found that ferroptosis appeared in tubular epithelial cells (TECs) of various human kidney diseases and the upregulation of tubular proferroptotic gene ACSL4 was correlated with renal function in patients with acute kidney tubular injury. XJB-5-131, which showed high affinity for TECs, attenuated I/R-induced renal injury and inflammation in mice by specifically inhibiting ferroptosis rather than necroptosis and pyroptosis. Single-cell RNA sequencing (scRNA-seq) indicated that ferroptosis-related genes were mainly expressed in tubular epithelial cells after I/R injury, while few necroptosis- and pyroptosis-associated genes were identified to express in this cluster of cell. Taken together, ferroptosis plays an important role in renal tubular injury and the inhibition of ferroptosis by XJB-5-131 is a promising therapeutic strategy for protection against renal tubular cell injury in kidney diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI