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Published on: March 14, 2019
Transcriptomic profiling and differential analysis reveal the renal toxicity mechanisms of mice under cantharidin
Xin Liu1, Linghan Zhang1, Wenchao Tang2
1Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Abstract:
Cantharidin (CTD), extracted from the traditional Chinese medicine mylabris, has shown significant curative effects against a variety of tumors, but its clinical application is limited by its high toxicity. Studies have revealed that CTD can cause toxicity in the kidneys; however, the underlying molecular mechanisms remain unclear. In this study, we investigated the toxic effects in mouse kidneys following CTD treatment by pathological and ultrastructure observations, biochemical index detection, and transcriptomics, and explored the underlying molecular mechanisms by RNA sequencing (RNA-seq). The results showed that after CTD exposure, the kidneys had different degrees of pathological damage, altered uric acid and creatinine levels in serum, and the antioxidant indexes in tissues were significantly increased. These changes were more pronounced at medium and high doses of CTD. RNA-seq analysis revealed 674 differentially expressed genes compared with the control group, of which 131 were upregulated and 543 were downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that many differentially expressed genes were closely related to the stress response, the CIDE protein family, and the transporter superfamily, as well as the MAPK, AMPK, and HIF-1 pathways. The reliability of the RNA-seq results was verified by qRT-PCR of the six target genes. These findings offer insight into the molecular mechanisms of renal toxicity caused by CTD and provide an important theoretical basis for the clinical treatment of CTD-induced nephrotoxicity.
Insights
Cantharidin (CTD) causes kidney toxicity, impacting uric acid and creatinine levels. This study reveals molecular mechanisms involving stress response and specific pathways, offering insights for treating CTD-induced nephrotoxicity.
Area of Science:
- Toxicology
- Molecular Biology
- Pharmacology
Background:
- Cantharidin (CTD), derived from traditional Chinese medicine, shows anti-tumor potential but is limited by significant kidney toxicity.
- The precise molecular mechanisms underlying CTD-induced nephrotoxicity are not fully understood.
- Understanding these mechanisms is crucial for safe clinical application of CTD.
Purpose of the Study:
- To investigate the pathological and molecular effects of Cantharidin (CTD) on mouse kidneys.
- To identify key genes, pathways, and biological processes involved in CTD-induced renal toxicity.
- To provide a theoretical foundation for managing CTD-related kidney damage.
Main Methods:
- Pathological and ultrastructure observations of kidney tissues.
- Biochemical index detection (uric acid, creatinine, antioxidant indexes).
- Transcriptomic analysis using RNA sequencing (RNA-seq) and qRT-PCR validation.
Main Results:
- CTD exposure induced varying degrees of kidney damage, elevated serum uric acid and creatinine, and increased tissue antioxidant indexes, particularly at higher doses.
- RNA-seq identified 674 differentially expressed genes (131 upregulated, 543 downregulated) compared to controls.
- Enrichment analyses linked these genes to stress response, CIDE protein family, transporter superfamily, and MAPK, AMPK, and HIF-1 pathways.
Conclusions:
- CTD exposure triggers significant renal toxicity through complex molecular mechanisms involving stress responses and specific signaling pathways.
- The identified molecular signatures provide critical insights into CTD-induced nephrotoxicity.
- This research lays the groundwork for developing strategies to mitigate CTD's adverse effects on the kidneys.
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