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MicroRNA In situ Hybridization for Formalin Fixed Kidney Tissues
Published on: November 30, 2013
Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis
Subham Dasgupta1, Tatiana Sharapova2, Prathap K Mahalingaiah2
1Department of Biological Sciences, Clemson University, Clemson, SC, USA.
Abstract:
Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys. Exosome-associated miRNA exhibited distinctive trends when compared to miRNAs quantified in whole urine, which may reflect a different urinary excretion mechanism of miRNAs than those released passively into the urine. Although further research and mechanistic studies are required to elucidate how these miRNAs regulate signaling in disease pathways, we present, for the first time, data that several miRNAs displayed strong correlations with histopathology scores, thus indicating their potential use as biomarkers to predict the development of DIKI in preclinical studies and clinical trials. Also, these findings can potentially be translated into other non-clinical species or human for the detection of DIKI.
Insights
Urinary microRNAs (miRNAs) show promise as early biomarkers for drug-induced kidney injury (DIKI). Specific miRNAs correlated with kidney damage in preclinical models, suggesting potential for early DIKI detection in clinical trials.
Area of Science:
- Nephrology
- Biomarker Discovery
- Pharmacology
Background:
- Drug-induced kidney injury (DIKI) is kidney damage from medications.
- Early detection of DIKI is crucial for patient outcomes.
- Urinary microRNAs (miRNAs) are being investigated as non-invasive biomarkers.
Purpose of the Study:
- Identify urinary miRNA biomarkers for predicting DIKI before clinical diagnosis.
- Evaluate specific miRNAs (miR-210-3p, -423-5p, -143-3p, -130b-3p, -486-5p, -193a-3p) as DIKI predictors.
- Compare exosome-associated miRNAs with whole urine miRNAs for DIKI detection.
Main Methods:
- Quantified six specific miRNAs in urinary samples from cynomolgus monkeys exposed to a nephrotoxicant.
- Analyzed miRNA levels across multiple time points post-exposure.
- Correlated miRNA levels with histopathology scores of kidney damage.
Main Results:
- Distinct trends observed between exosome-associated miRNAs and whole urine miRNAs.
- Several urinary miRNAs showed strong correlations with kidney histopathology scores.
- These findings suggest potential predictive value for specific miRNAs in DIKI.
Conclusions:
- Urinary miRNAs, particularly exosome-associated ones, may serve as early predictive biomarkers for DIKI.
- The identified miRNAs hold potential for preclinical and clinical applications in DIKI detection.
- Further research is needed to elucidate miRNA mechanisms in DIKI pathogenesis.

