title: Glomerulonephritis-Induced Changes in Urinary and Kidney MicroRNA Profiles in Rats.
abstract: MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and thus are involved in various physiological and pathological states. Due to their stability in biofluids miRNAs have also been proposed as biomarkers (BMs) for tissue injury. We investigated the usefulness of urinary miRNAs for detection of site-specific renal damage in an antiglomerular basement membrane glomerulonephritis (GN) model in rats by comparing GN-induced urinary miRNAs profiles to traditional and newer protein BMs, and to proximal tubular injury-induced urinary miRNA profiles observed previously after cisplatin (Cp) treatment. Male Wistar Kyoto and Sprague Dawley rats were dosed once with 1, 2.5, and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. Although serum creatinine and BUN were not changed, several protein BMs and 74 urinary miRNAs were found to be increased 8 and 14 days after NTS administration. Of these 74 miRNAs, 5 were identified as increased after NTS but not after Cp treatment. Using in situ hybridization two of them, miR-10 b and -100, were found to be localized in distal segments of the nephron, potentially reflecting the tubular injury in those regions. Furthermore, evaluation of both miRNA and mRNA expression in the kidney revealed possible miRNA-mRNA interactions mostly associated with fibrotic and transforming growth factor β signaling. In conclusion, our investigations support the potential of urinary miRNAs as specific BMs for kidney injury, and suggest a role of miRNAs in pathological processes during GN in the kidney.
authors.affiliation: *Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany, Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, Massachusetts, Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany and Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany *Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany, Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, Massachusetts, Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany and Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Pavkovic
authors.affiliation: *Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany, Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, Massachusetts, Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany and Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Riefke
authors.affiliation: *Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany, Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, Massachusetts, Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany and Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Frisk
authors.affiliation: *Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany, Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, Massachusetts, Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany and Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Gröticke
authors.affiliation: *Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany, Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, Massachusetts, Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany and Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany heidrun.ellinger-ziegelbauer@bayer.com.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Ellinger-Ziegelbauer
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000652:urine; D000818:Animals; D001706:Biopsy; D002945:Cisplatin; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000652:urine*; D017403:In Situ Hybridization; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000652:urine; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D005819:Genetic Markers; C000603309:MIRN10 microRNA, rat; C577629:MIRN100 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D002945:Cisplatin
keywords: biomarker; glomerulonephritis; urinary microRNAs