Data from:Investigation of urinary miRNA profile changes in amphotericin B-induced nephrotoxicity in C57BL/6 mouse, Sprague-Dawley rats and beagle dogs
Data files
Feb 28, 2025 version files 5.08 MB
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README.md
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Supplemantary_Table_1.csv
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Supplemantary_Table_2.csv
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Supplementary_Figure_1.tif
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Supplementary_Figure_2.tif
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Supplementary_Figure_3.tif
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Supplementary_Table_3_(mouse_raw_data).xlsx
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Supplementary_Table_4_(rat_raw_data).xlsx
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Supplementary_Table_5_(Dog_raw_data).xlsx
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Abstract
MicroRNA (miRNAs) have been associated with drug-induced kidney injury (DIKI). However, there are few reports on the utility of miRNAs, when monitoring for nephrotoxicity across multiple species. The purpose of this study was to assess the value of urinary miRNA profile changes as renal safety biomarkers, when monitoring for kidney injury in investigative toxicology studies. To this end, we evaluated urine miRNA expression levels in response to amphotericin B (AmpB-induced nephrotoxicity in mice, rats, and dogs. The results showed that 35 miRNAs were significantly differentially expressed across the three species in response to the induced renal injuries. Dogs showed the highest number of miRNAs with significant changes. miR-205-5p and miR-31-5p were the most consistently altered miRNA biomarkers across all three species. In rodents, these two miRNAs were the most sensitive markers and showed comparable or better sensitivities than the previously published urine protein biomarkers with the same nephrotoxicant. In dogs, none of the upregulated miRNAs were as sensitive as urine clusterin protein as observed in a previously published study with AmpB. Taken together, these miRNAs could complement the more established urinary protein biomarkers in monitoring DIKI in mice, rats, and dogs. To our knowledge, this is the first report that demonstrates the comparative utility of urinary miRNAs for the early detection of DIKI across three nonclinical animal models.
https://doi.org/10.5061/dryad.c59zw3rk4
Description of the data and file structure
The purpose of this study was to assess the value of urinary miRNA profile changes as biomarkers, when monitoring for kidney injury in investigative toxicology studies. To this end, we evaluated urine miRNA response to amphotericin B-induced nephrotoxicity in mice, rats, and dogs. The results showed that there were 35 miRNAs that were significantly differentially expressed across all species in response to the renal injuries, with dogs having the highest number of miRNAs with significant changes. miR-205-5p and miR-31-5p were the most consistent miRNA biomarkers across all 3 species and were also the most sensitive markers in mice and rats. In rodents, these two miRNAs had comparable or better sensitivities than the previously published urine protein biomarkers with the same nephrotoxicant. In dogs, none of the upregulated miRNAs were as sensitive as urine clusterin as observed in a previously published study with the same nephrotoxicant. Taken together, these miRNAs could complement the more established urinary protein biomarkers in monitoring DIKI. To our knowledge, this is the first report that demonstrates the comparative utility of urinary miRNAs for the early detection of DIKI across three nonclinical animal species.
The supplementary files submitted included:
1) Supplementary Figures 1-3: the heatmaps showing the the hierarchical clustering of the miRNAs evaluated, whose average expression was higher than the calculated limit of detection of the assay for mice, rats and dogs samples have been provided.
2) Supplementary Tables 1-2: The fraction of samples detecting a given miRNA above the calculated limit of detection for rodents and dogs samples.
3) Supplementary Tables 3-5: The raw data used for the data analyses and interpretations.
Files and variables
- Supplementary Table 1.csv: The fraction of samples detecting a given miRNA above the calculated limit of detection in rodents.
- Supplementary Table 2.csv: The fraction of samples detecting a given miRNA above the calculated limit of detection in dogs.
- Supplementary Table 3.xlsx: The raw data used for data analyses and interpretations for mice
- Supplementary Table 4.xlsx: The raw data used for data analyses and interpretations for rats
- Supplementary Table 5.xlsx: The raw data used for data analyses and interpretations for dogs
- Supplementary Figure 1.tif: The heatmap showing the hierarchical clustering of the miRNAs evaluated, whose average expression was higher than the calculated limit of detection of the assay for all mice samples
- Supplementary Figure 2.tif: The heatmap showing the hierarchical clustering of the miRNAs evaluated, whose average expression was higher than the calculated limit of detection of the assay for all rats samples
- Supplementary Figure 3.tif: The heatmap showing the hierarchical clustering of the miRNAs evaluated, whose average expression was higher than the calculated limit of detection of the assay for all dogs samples