title: Identification of urinary microRNA biomarkers for detection of gentamicin-induced acute kidney injury in rats.
abstract: MicroRNAs (miRNAs) have been recently recognized as promising non-invasive biomarkers for detecting the organ injuries. To further understand the sensibility and reliability of miRNA measurements in urine sample for predicting drug-induced early nephrotoxicity, a global urinary miRNA expression analysis was performed in the rodent models with gentamicin-induced acute kidney injury (AKI). Male Wistar rats were daily administrated with gentamicin (0, 60, and 120 mg/kg) for up to 10 days by intraperitoneal injection, and the miRNA profiling of animal urine samples were subsequently analyzed using TaqMan(®) Array Rodent miRNA Cards. The results showed that four miRNAs (mmu-miR-138-5p, mmu-miR-1971, mmu-miR-218-1-3p, and rno-miR-489) were continuously increased in urine samples since day 4 after administration with gentamicin, which was not reflected by the standard markers such as serum creatinine (Cr) and urea nitrogen (BUN). Furthermore, other nine urinary miRNAs were increased in both 60 and 120 mg/kg groups on day 8. Receiver operator characteristics analysis demonstrated that the performance of these miRNAs with time- or dose-dependent increases were comparable to standard biomarkers (i.e. serum Cr and BUN), suggesting that the urinary miRNA panel can be used as potential biomarkers for the detection of gentamicin-induced AKI in rats. Moreover, the computer prediction analysis showed that these differentially expressed miRNAs were potentially targeted to many genes, which were mainly associated with the regulation of metabolic process and signaling. These data will improve the understanding and prediction of toxicology processes induced by nephrotoxicants.
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Qu
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huo
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China.
authors.forename: Jufeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Center for Safety Evaluation of Drugs, National Institutes of Food and Drug Control, Hongda Middle Street A8, Beijing Economic and Technological Development Area, Beijing, 100176, China. Electronic address: libo@nifdc.org.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000652:urine*; D000818:Animals; D019540:Area Under Curve; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005819:Genetic Markers; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*; D011237:Predictive Value of Tests; D012372:ROC Curve; D017208:Rats, Wistar; D018570:Risk Assessment; D013997:Time Factors; D043922:Toxicogenetics / Q000379:methods*; D016482:Urinalysis
chemical_list: D005819:Genetic Markers; D005839:Gentamicins; D035683:MicroRNAs
keywords: Gentamicin; Nephrotoxicity; Rats; Urinary biomarkers; microRNA