title: MicroRNA signatures associated with thioacetamide-induced liver fibrosis in mice.
abstract: Multiple etiologies of liver injury are associated with fibrosis in which the key event is the activation of hepatic stellate cells (HSCs). Although microRNAs (miRNAs) are reportedly involved in fibrogenesis, the complete array of miRNA signatures associated with the disease has yet to be elucidated. Here, deep sequencing analysis revealed that compared to controls, 80 miRNAs were upregulated and 21 miRNAs were downregulated significantly in the thioacetamide (TAA)-induced mouse fibrotic liver. Interestingly, 58 of the upregulated miRNAs were localized to an oncogenic miRNA megacluster upregulated in liver cancer. Differential expression of some of the TAA-responsive miRNAs was confirmed, and their human orthologs were similarly deregulated in TGF-β1-activated HSCs. Moreover, a functional analysis of the experimentally validated high-confidence miRNA targets revealed significant enrichment for the GO terms and KEGG pathways involved in HSC activation and liver fibrogenesis. This is the first comprehensive report of miRNAs profiles during TAA-induced mouse liver fibrosis.
authors.affiliation: a College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.|b Institute of Animal Molecular Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Jae-Sang
authors.initials: JS
authors.lastname: Hong
authors.affiliation: a College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.|b Institute of Animal Molecular Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Do-Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: a College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.|b Institute of Animal Molecular Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Ye Won
authors.initials: YW
authors.lastname: Yook
authors.affiliation: c School of Integrative Engineering , Chung-Ang University , Seoul , Republic of Korea.
authors.forename: Dokyun
authors.initials: D
authors.lastname: Na
authors.affiliation: a College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.|b Institute of Animal Molecular Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: a College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.|b Institute of Animal Molecular Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: a College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.|b Institute of Animal Molecular Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Young Sik
authors.identifier: http://orcid.org/0000-0002-6709-3809
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D015398:Signal Transduction; D013853:Thioacetamide; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000199:Actins; C000619309:Col1a2 protein, mouse; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D013853:Thioacetamide
keywords: deep sequencing; liver fibrosis; microRNA; thioacetamide