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A Single-Cell Transcriptome Profiling of Triptolide-Induced Nephrotoxicity in Mice.
Jiangpeng Wu1,2, Jinan Guo2, Siyu Xia2
1School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Advanced Biology
|June 12, 2024
Summary
Triptolide (TP) causes kidney damage by harming various kidney cells and activating immune responses. This study reveals TP-induced nephrotoxicity mechanisms at the single-cell level, offering insights for potential treatments.
Area of Science:
- Nephrology
- Toxicology
- Immunology
Background:
- Triptolide (TP), from Tripterygium wilfordii Hook F (TWHF), has anti-inflammatory potential.
- TP's nephrotoxicity is a concern, with mechanisms poorly understood at single-cell resolution.
Purpose of the Study:
- To elucidate the mechanisms of Triptolide-induced nephrotoxicity using single-cell RNA sequencing.
- To characterize the renal cell atlas response to TP treatment.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of kidney tissues from control and TP-treated mice.
- Analysis of heterogeneous cellular responses, including epithelial cells, endothelial cells, fibroblasts, and immune cells.
- Ligand-receptor crosstalk analysis to identify key signaling pathways.
Main Results:
- TP induces heterogeneous responses in nephron epithelial cells, linked to oxidative stress and inflammation.
- TP disrupts vascular function and damages fibroblasts.
- TP causes immune cell damage and activates pro-inflammatory Macro_C1 cells, potentially via the SPP1 pathway.
Conclusions:
- This study provides a comprehensive single-cell resolution map of TP-associated nephrotoxicity.
- Findings enhance understanding of TP-induced kidney damage pathogenesis.
- Identifies potential therapeutic targets for mitigating TP nephrotoxicity.
