title: Anti-fibrotic Role of miR-214 in Thioacetamide-induced Liver Cirrhosis in Rats.
abstract: An increasing number of studies have focused on the role of microRNAs in liver fibrosis/cirrhosis. miR-214 has recently attracted more attention as a fibrosis-related factor; however, the molecular mechanisms in hepatic fibrogenesis remain largely unknown. Here, we investigate the pathological role of miR-214 during progression of liver cirrhosis in rats. Rats were injected intraperitoneally with thioacetamide at a dose of 100 mg/kg body weight, twice a week. The liver was collected at post first injection weeks 5, 10, 15, and 20. Hepatic expression of miR-214 was analyzed by real-time polymerase chain reaction, in situ hybridization, and laser microdissection. The effects of miR-214 overexpression were investigated by in vitro transfection using fibroblastic MT-9 cells. miR-214 was highly upregulated in the fibrotic area in parallel with the cirrhosis progression. miR-214 overexpression in MT-9 cells under transforming growth factor-β1 stimulation resulted in decreased cell number and increased expression of cleaved caspase 3 and decreased expression of α-smooth muscle actin, suggesting that miR-214 induces apoptosis and inhibits myofibroblast differentiation in fibroblastic cells under stimulation of fibrogenic factors. These data indicate an anti-fibrotic role of miR-214 in chemically induced liver fibrosis/cirrhosis.
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan Both Takeshi Izawa and Takashi Horiuchi contributed equally to the article. izawa@vet.osakafu-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan Both Takeshi Izawa and Takashi Horiuchi contributed equally to the article.
authors.forename: Takashi
authors.initials: T
authors.lastname: Horiuchi
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan.
authors.forename: Machi
authors.initials: M
authors.lastname: Atarashi
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002460:Cell Line; D018450:Disease Progression; D005355:Fibrosis / Q000188:drug therapy*; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D013853:Thioacetamide; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D053148:Caspase 3; D035683:MicroRNAs; D013853:Thioacetamide; D053773:Transforming Growth Factor beta1; C559947:Mirn214 microRNA, rat; C498862:Acta2 protein, rat
keywords: anti-fibrotic role; liver cirrhosis; miR-214; microRNA; rat; thioacetamide.