title: Time-course changes in the expression levels of miR-122, -155, and -21 as markers of liver cell damage, inflammation, and regeneration in acetaminophen-induced liver injury in rats.
abstract: Drug-induced liver injury (DILI) is a significant threat to patient health and a major concern during drug development. Recently, multiple circulating microRNAs (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and validate miRNAs for clinical use, we investigated the time-course changes in miR-122 expression levels in an acetaminophen-induced liver injury model in rats. In addition, miR-155 and miR-21 were evaluated as makers of inflammation and regeneration, respectively, to characterize liver status. Our results revealed that miR-122 is an early and sensitive biomarker of hepatocellular injury at a stage when alanine transaminase, aspartate transaminase, and total bilirubin were not detectable. However, no significant differences in the expression levels of other miRNAs (miR-155 and -21) were observed between treatment and vehicle groups. Collectively, these time-course changes in the expression levels of miRNAs may be useful as markers for clinical decision-making, in the diagnosis and treatment of DILI.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Park
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Woori
authors.initials: W
authors.lastname: Jo
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Sungwoong
authors.initials: S
authors.lastname: Jang
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Ryu
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Hyo-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Eun-Sil
authors.initials: ES
authors.lastname: Yu
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D008115:Liver Regeneration; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D011237:Predictive Value of Tests; D051381:Rats; D013995:Time
chemical_list: D015415:Biomarkers; C580643:MIRN122 microRNA, rat; C580597:MIRN155 microRNA, rat; D035683:MicroRNAs; D000082:Acetaminophen
keywords: acetaminophen; drug-induced liver injury; miR-122; miR-155; miR-21