Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage.

Autor: Wolenski FS; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Shah P; Molecular Pathology, Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Sano T; Drug Safety Research Laboratories, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, 251-8555, Japan., Shinozawa T; Drug Safety Research Laboratories, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, 251-8555, Japan., Bernard H; Molecular Pathology, Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Gallacher MJ; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Wyllie SD; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Varrone G; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Cicia LA; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Carsillo ME; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Fisher CD; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Ottinger SE; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Koenig E; Molecular Pathology, Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA., Kirby PJ; Drug Safety Research & Evaluation, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, 02139, USA.
Jazyk: angličtina
Zdroj: Journal of applied toxicology : JAT [J Appl Toxicol] 2017 Mar; Vol. 37 (3), pp. 278-286. Date of Electronic Publication: 2016 Jul 11.
DOI: 10.1002/jat.3358
Abstrakt: MicroRNAs (miRNA) are short single-stranded RNA sequences that have a role in the post-transcriptional regulation of genes. The identification of tissue specific or enriched miRNAs has great potential as novel safety biomarkers. One longstanding goal is to associate the increase of miRNA in biofluids (e.g., plasma and urine) with tissue-specific damage. Next-generation sequencing (miR-seq) was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (acetaminophen [APAP] or carbon tetrachloride [CCL 4 ]). Analyses with traditional serum chemistry and histopathology confirmed that toxicant-induced organ damage was specific. In animals treated with cisplatin, levels of five miRNAs were significantly altered in the kidney, 14 in plasma and six in urine. In APAP-treated animals, five miRNAs were altered in the liver, 74 in plasma and six in urine; for CCL 4 the changes were five, 20 and 6, respectively. Cisplatin treatment caused an elevation of miR-378a in the urine, confirming the findings of other similar studies. There were 17 in common miRNAs elevated in the plasma after treatment with either APAP or CCL 4 . Four of these (miR-122, -802, -31a and -365) are known to be enriched in the livers of rats. Interestingly, the increase of serum miR-802 in both hepatotoxicant treatments was comparable to that of the well-known liver damage marker miR-122. Taken together, comparative analysis of urine and plasma miRNAs demonstrated their utility as biomarkers of organ injury. Copyright © 2016 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.
(Copyright © 2016 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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