title: Identification of Promising Urinary MicroRNA Biomarkers in Two Rat Models of Glomerular Injury.
abstract: 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.
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development; rounak.nassirpour@pfizer.com.
authors.forename: Rounak
authors.initials: R
authors.lastname: Nassirpour
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Homer
authors.affiliation: Business Technology, Pfizer Research and Development, Andover, Massachusetts 01810; and.
authors.forename: Sachin
authors.initials: S
authors.lastname: Mathur
authors.affiliation: Business Technology, Pfizer Research and Development, Andover, Massachusetts 01810; and.
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Drug Safety, Pfizer Research and Development, Groton, Connecticut 06340.
authors.forename: Tom
authors.initials: T
authors.lastname: Brown
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Deborah
authors.initials: D
authors.lastname: Carraher
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: James
authors.initials: J
authors.lastname: Warneke
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Steven
authors.initials: S
authors.lastname: Bailey
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Karen
authors.initials: K
authors.lastname: Percival
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Shawn P
authors.initials: SP
authors.lastname: O'Neil
authors.affiliation: *Drug Safety, Pfizer Worldwide Research and Development;
authors.forename: Laurence O
authors.initials: LO
authors.lastname: Whiteley
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D015433:Glomerulonephritis, Membranous / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D026541:Heymann Nephritis Antigenic Complex / Q000737:chemistry; D007106:Immune Sera / Q000633:toxicity; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D061346:Laser Capture Microdissection; D008297:Male; D055432:Metabolomics / Q000379:methods; D035683:MicroRNAs / Q000378:metabolism / Q000652:urine*; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D034561:Sheep, Domestic
chemical_list: D015415:Biomarkers; D026541:Heymann Nephritis Antigenic Complex; D007106:Immune Sera; D035683:MicroRNAs; D011692:Puromycin Aminonucleoside
keywords: Heymann nephritis; biomarker; glomerular injury; microRNA; puromycin; urine