XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia-reperfusion injury.
Zhi ZhaoJianliang WuHuzi XuCheng ZhouBicui HanHan ZhuZhizhi HuZhimei MaZhang-Yin MingYing YaoRui ZengGang XuPublished in: Cell death & disease (2020)
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.
Keyphrases
- cell death
- high glucose
- single cell
- endothelial cells
- acute kidney injury
- chronic kidney disease
- rna seq
- oxidative stress
- cell cycle arrest
- ischemia reperfusion injury
- genome wide
- signaling pathway
- cardiac surgery
- cell therapy
- stem cells
- metabolic syndrome
- cell proliferation
- poor prognosis
- mesenchymal stem cells
- peritoneal dialysis
- high fat diet induced