title: Changes in the expression of miRNAs at the pericentral and periportal regions of the rat liver in response to hepatocellular injury: comparison with the changes in the expression of plasma miRNAs.
abstract: MicroRNAs (miRNAs) in body fluids have received attention as potential biomarkers of organ damage because miRNAs that are highly or specifically expressed in a given organ are likely released into body fluids as a result of damage to that organ. We previously determined that the plasma miRNA profile in rats was dramatically changed due to acetaminophen (APAP)-induced pericentral necrosis and methapyrilene (MP)-induced periportal necrosis in the liver. The purpose of this study was to examine whether the expression of hepatic miRNAs is differentially modulated at different zones due to injury and to examine the relationship of the hepatic miRNA profile with the changes in the plasma miRNA expression profile. Through the laser microdissection of the periportal and periportal regions of the liver and TaqMan microRNA Array analysis, we found that 49 miRNAs are differentially expressed between the pericentral and periportal regions of control rats. In both APAP- and MP-treated rats, the miRNAs that presented decreased expression dominated in both the injured and non-injured areas compared with the miRNAs that exhibited increased expression. The changes in miRNA expression in each region of the liver were compared with those observed in the plasma. Of the 301 plasma miRNAs with expression that was changed as a result of APAP administration, only 21% were changed in the injured area of the liver. Of the 263 plasma miRNAs with expression that was changed due to MP administration, only 24% were changed in the injured area of the liver. Thus, the miRNA expression profiles in the plasma do not merely reflect the release of miRNAs from the damaged cells in the liver. This report provides the first demonstration of zonal miRNA expression in the liver and of the relationship of the miRNA expression profile in a tissue with the plasma miRNA profile.
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamaura
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address: nmiki@p.kanazawa-u.ac.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tatsumi
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Fukami
authors.affiliation: Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Sugitani, Toyama 930-0194, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000097:blood; D042282:Microdissection; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D018076:DNA, Complementary; D035683:MicroRNAs; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Biomarker; Liver injury; MicroRNA; Zonal expression