Urinary microRNAs miR-15b and miR-30a as novel noninvasive biomarkers for gentamicin-induced acute kidney injury

• Published in: Toxicology letters 2021-03, Vol.338, p.105-113
• Main Authors: Sun, B., Qu, Z., Cheng, G.L., Yang, Y.W., Miao, Y.F., Chen, X.G., Zhou, X.B., Li, B.
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Acute Kidney Injury - genetics; Acute Kidney Injury - pathology; Acute Kidney Injury - urine; Animals; Beagle dog; Biomarker; Biomarkers - urine; Disease Models, Animal; Dogs; Gene Expression Regulation; Gentamicin; Gentamicins; High-Throughput Nucleotide Sequencing; microRNA; MicroRNAs - genetics; MicroRNAs - urine; Real-Time Polymerase Chain Reaction; RNA sequencing; Sequence Analysis, RNA; Time Factors
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2020.12.006

[Display omitted] •Gentamicin (40 mg/kg) exposure induced minimal or mild kidney injury in beagle dogs for consecutive 12-days.•A total of 117 dys-regulated miRNAs were identified and visualized in a heatmap among the treatment day 0, 3, 6, and 12 using RNA sequencing.•Six top up-regulated and down-regulated microRNAs were screened and validated using RT-qPCR.•miR-15b and -15b-3p were superior to urinary kidney injury molecule-1using ROC curve assays.•Levels of miR-15b and -30a in urine were significantly correlated with those in kidney tissue. MicroRNAs serve as potential biomarkers in various pathological models, and are stable and detectable in biofluids. We investigated the urinary microRNA expression profile in a gentamicin-induced acute kidney injury canine model using RNA sequencing. A total of 234 differentially expressed microRNAs were screened after 12 consecutive days of gentamicin administration (P < 0.05). Six candidate microRNAs (miR-15b, -15b-3p, -16, -30a, -30a-3p, and -30c-2-3p) were selected according to a set criterion, and validated by real-time quantitative PCR. The diagnostic values of these six candidate microRNAs were better than the traditional serum biomarkers (all P < 0.05). Further, using receiver operating characteristic curve analysis, we found that miR-15b and -15b-3p were superior to urinary kidney injury molecule-1 (both P < 0.05). Moreover, miR-15b and -30a levels in the urine samples significantly correlated with their respective levels in the kidney tissue samples (r=0.512 and 0.505, respectively, both P < 0.05). Our data concluded that miR-15b and -30a may be promising biomarkers for renal toxicity.