title: MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells.
abstract: MicroRNA-122 (miR-122) is one of the most abundant miRs in the liver. Previous studies have demonstrated that miR-122 plays a role in inflammation in the liver and functions in hepatic stellate cells (HSCs), which reside in the space of Disse. Here, we showed that the transient inhibition of PKR-activating protein (PACT) expression, by miR-122 or siRNA targeting of PACT, suppressed the production of proinflammatory cytokines, such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and IL-1β, in human HSC LX-2. Sequence and functional analyses confirmed that miR-122 directly targeted the 3'-untranslated region of PACT. Immunofluorescence analysis revealed that miR-122 blocked NF-κB-nuclear translocation in LX-2 cells. We also showed that conditioned medium from miR-122-transfected LX-2 cells suppressed human monocyte-derived THP-1 cell migration. Taken together, our study indicates that miR-122 may downregulate cytokine production in HSCs and macrophage chemotaxis and that the targeting of miR-122 may have therapeutic potential for preventing the progression of liver diseases.
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Haga
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.|Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000235:genetics; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins