Identification of Promising Urinary MicroRNA Biomarkers in Two Rat Models of Glomerular Injury

• DOI: 10.1093/toxsci/kfv167
• Publication Date: 2015-08-08T02:10:15Z
• Authors: Rounak Nassirpour; Bruce L. Homer; Sachin Mathur; Yizheng Li; Zhonghan Li; Tom Brown; Deborah Carraher; James Warneke; Steven Bailey; Karen Percival; Shawn P. O’Neil; Laurence O. Whiteley
• Keywords: Male; 0303 health sciences; Podocytes; Immune Sera; Kidney Glomerulus; Heymann Nephritis Antigenic Complex; Laser Capture Microdissection; Acute Kidney Injury; Puromycin Aminonucleoside; Glomerulonephritis, Membranous; Rats, Sprague-Dawley; Disease Models, Animal; MicroRNAs; Oxidative Stress; 03 medical and health sciences; Gene Expression Regulation; Microscopy, Electron, Transmission; Disease Progression; Animals; Metabolomics; Biomarkers; Sheep, Domestic

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate protein levels posttranscriptionally. miRNAs play important regulatory roles in many cellular processes and have been implicated in several diseases. Recent studies have reported significant levels of miRNAs in a variety of body fluids, raising the possibility that miRNAs could serve as useful biomarkers. Here, changes in miRNA expression patterns are described in 2 different rodent models of glomerular injury (acute puromycin aminonucleoside nephropathy and passive Heymann nephritis). By employing 2 different modes of glomerular insult, oxidative stress and immune-mediated toxicity, miRNA changes in both isolated glomeruli as well as urine specimens allow for identification of urinary miRNA biomarkers that are suggestive of drug-induced injury specifically to the glomerulus. Subsets of glomerular urinary miRNAs associated with these different modes of glomerular toxicity seem to be dependent on the mechanism of the induced injury, while 9 miRNAs that changed early in both glomerular and urine specimens were common to both studies. We further show that the miRNAs identified as mechanism-specific early glomerular injury biomarkers target key pathways and transcripts relevant to the type of insult, while the insult-independent changes might serve as ideal glomerular injury biomarkers.