学術雑誌論文 Inhibition of microRNA-214 ameliorates hepatic fibrosis and tumor incidence in platelet-derived growth factor C transgenic mice

Okada, Hikari  ,  Honda, Masao  ,  Campbell, Jean S.  ,  Takegoshi, Kai  ,  Sakai, Yoshio  ,  Yamashita, Taro  ,  Shirasaki, Takayoshi  ,  Takabatake, Riuta  ,  Nakamura, Mikiko  ,  Tanaka, Takuji  ,  Kaneko, Shuichi

106 ( 9 )  , pp.1143 - 1152 , 2015-09-01 , Japanese Cancer Association / Blackwell Publishing Ltd
ISSN:1347-9032
NII書誌ID(NCID):AA11808050
内容記述
Differentially regulated microRNA (miRNA) are associated with hepatic fibrosis; however, their potential usefulness for blocking hepatic fibrosis has not been exploited fully. We examined the expression of miRNA in the liver of a transgenic mouse model in which platelet-derived growth factor C (PDGF-C) is overexpressed (Pdgf-c Tg), resulting in hepatic fibrosis and steatosis and the eventual development of hepatocellular carcinoma (HCC). Robust induction of miR-214 correlated with fibrogenesis in the liver of Pdgf-c Tg mice, atherogenic high-fat diet-induced NASH mice, and patients with chronic hepatitis B or C. Pdgf-c Tg mice were injected with locked nucleic acid (LNA)-antimiR-214 via the tail vein using Invivofectamine 2.0 and the degree of hepatic fibrosis and tumor incidence were evaluated. Pdgf-c Tg mice treated with LNA-antimiR-214 showed a marked reduction in fibrosis and tumor incidence compared with saline or LNA-miR-control-injected control mice. In vitro, LNA-antimiR-214 significantly ameliorated TGF-β1-induced pro-fibrotic gene expression in Lx-2 cells. MiR-214 targets a negative regulator of EGFR signaling, Mig-6. Mimic-miR-214 decreased the expression of Mig-6 and increased the levels of EGF-mediated p-EGFR (Y1173 and Y845) and p-Met (Tyr1234/1235) in Huh-7 cells. Conversely, LNA-antimiR-214 repressed the expression of these genes. In conclusion, miR-214 appears to participate in the development of hepatic fibrosis by modulating the EGFR and TGF-β signaling pathways. LNA-antimiR-214 is a potential therapy for the prevention of hepatic fibrosis. MiR-214 appears to participate in the development of hepatic fibrosis by modulating EGFR and TGF-β signaling pathways. LNA-anti-miR-214 may be a potentially therapy in the prevention of hepatic fibrosis. © 2015 Japanese Cancer Association.
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http://dspace.lib.kanazawa-u.ac.jp/dspace/bitstream/2297/45964/1/ME-PR-HONDA-M-1143.pdf

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