A Single‐Cell Transcriptome Profiling of Triptolide‐Induced Nephrotoxicity in Mice

作者：Jiangpeng Wu, Jinan Guo, Siyu Xia, Jiayun Chen, Min Cao, Lulin Xie, Chuanbin Yang, Feng Qiu, Jigang Wang · 发表于：Advanced Biology · 年份：2024 · DOI：10.1002/adbi.202400120 · 被引用次数：4 · 研究领域：Natural Compounds in Disease Treatment、Glioma Diagnosis and Treatment

Triptolide (TP), an active component isolated from the traditional Chinese herb Tripterygium wilfordii Hook F (TWHF), shows great promise for treating inflammation-related diseases. However, its potential nephrotoxic effects remain concerning. The mechanism underlying TP-induced nephrotoxicity is inadequately elucidated, particularly at single-cell resolution. Hence, single-cell RNA sequencing (scRNA-seq) of kidney tissues from control and TP-treated mice is performed to generate a thorough description of the renal cell atlas upon TP treatment. Heterogeneous responses of nephron epithelial cells are observed after TP exposure, attributing differential susceptibility of cell subtypes to excessive reactive oxygen species and increased inflammatory responses. Moreover, TP disrupts vascular function by activating endothelial cell immunity and damaging fibroblasts. Severe immune cell damage and the activation of pro-inflammatory Macro_C1 cells are also observed with TP treatment. Additionally, ligand-receptor crosstalk analysis reveals that the SPP1 (osteopontin) signaling pathway targeting Macro_C1 cells is triggered by TP treatment, which may promote the infiltration of Macro_C1 cells to exacerbate renal toxicity. Overall, this study provides comprehensive information on the transcriptomic profiles and cellular composition of TP-associated nephrotoxicity at single-cell resolution, which can strengthen the understanding of the pathogenesis of TP-induced nephrotoxicity and provide...