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

Wu, Jiangpeng1,2,3; Guo, Jinan2,3; Xia, Siyu2,3; Chen, Jiayun4,5; Cao, Min2,3; Xie, Lulin2,3; Yang, Chuanbin2,3; Qiu, Feng1; Wang, Jigang1,2,3,4,5,6

2024-06-01

10.1002/adbi.202400120

ADVANCED BIOLOGY   影响因子和分区

2701-0198

["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 valuable clues for the discovery of new therapeutic targets to ameliorate TP-associated nephrotoxicity.","This study reveals the cellular composition and transcriptomic profile upon TP treatment at single-cell resolution. PT-S1 and PT-S3 cells show increased inflammatory response and apoptosis. TP disrupts vascular function by activating endothelial cell immunity and damaging fibroblasts. TP induces the activation of pro-inflammatory Macro_C1 cells. The SPP1 signaling pathway can promote the infiltration of Macro_C1 cells, thereby exacerbating renal toxicity. image"]

inflammatory response pharmacology single-cell RNA sequencing spp1, triptolide

SCI ; EI

英语

通讯

National Key Research and Development Program of China["2022YFC2303600","2020YFA0908000"] ; National Natural Science Foundation of China["82201786","82173914"] ; CACMS Innovation Fund["CI2021A05101","CI2021A05104"] ; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences[CI2021B014] ; Science and Technology Foundation of Shenzhen["JCYJ20220818102613029","JCYJ20210324114014039","JCYJ20210324115800001"] ; Guangdong Basic and Applied Basic Research Foundation["2020A1515110549","2021A1515110646"] ; National Key R&D Program of China Key projects for international cooperation on science, technology and innovation[2020YFE0205100] ; Fundamental Research Funds for the Central Public Welfare Research Institutes["ZZ14-YQ-050","ZZ14-YQ-051","ZZ14-YQ-052","ZZ14-FL-002","ZZ14-ND-010","ZZ15-ND-10"] ; null[ZYYCXTD-C-202002]

Materials Science

Materials Science, Biomaterials

WOS:001243938900001

WILEY-V C H VERLAG GMBH

Web of Science

1.Tianjin Univ Tradit Chinese Med, Sch Chinese Mat Med, Tianjin 301617, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Clin Med Coll 2, Jinan Univ,Affiliated Hosp 1,Dept Urol, Shenzhen 518020, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Clin Res Ctr Geriatr, Shenzhen Peoples Hosp, Clin Med Coll 2,Affiliated Hosp 1,Jinan Univ, Shenzhen 518020, Peoples R China
4.China Acad Chinese Med Sci, State Key Lab Qual Ensurance & Sustainable Use Dao, Artemisinin Res Ctr, Beijing 100700, Peoples R China
5.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
6.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China

Wu, Jiangpeng,Guo, Jinan,Xia, Siyu,et al. A Single-Cell Transcriptome Profiling of Triptolide-Induced Nephrotoxicity in Mice[J]. ADVANCED BIOLOGY,2024.

Wu, Jiangpeng.,Guo, Jinan.,Xia, Siyu.,Chen, Jiayun.,Cao, Min.,...&Wang, Jigang.(2024).A Single-Cell Transcriptome Profiling of Triptolide-Induced Nephrotoxicity in Mice.ADVANCED BIOLOGY.

Wu, Jiangpeng,et al."A Single-Cell Transcriptome Profiling of Triptolide-Induced Nephrotoxicity in Mice".ADVANCED BIOLOGY (2024).