Suppression of collagen synthesis by Dicer gene silencing in hepatic stellate cells

Molecular Medicine Reports
Fujun YuPeihong Dong

Abstract

MicroRNAs (miRNAs) have emerged as important mediators of hepatic stellate cells (HSCs) and are pivotal in the pathogenesis of liver fibrosis. Dicer, the key enzyme in the RNA interference (RNAi) pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence has demonstrated that Dicer expression is dysregulated in embryo development and tumors. In the present study, we aimed to address whether Dicer expression was correlated with the activity of HSCs. We used a recombinant lentivirus to generate short hairpin RNAs (shRNAs) targeting Dicer. The mRNA and protein expression of Dicer was effectively inhibited by three pairs of Dicer shRNA vectors, of which the shRNA1 vector exhibited the strongest inhibitory effect. The shRNA1 vector demonstrated a marked inhibitory effect on the activity of HSCs, resulting in the reduction of cell proliferation and the decrease of fibrosis-related genes, including type Ⅰ collagen (Col1A1), α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinases (TIMP). The mRNA expression of Col1A1, α-SMA and TIMP were decreased by 60, 56 and 49%, respectively. The protein expression was reduced by 56, 52 and 42%, respectively. Additionally, the inhibition of Dic...Continue Reading

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Citations

May 9, 2014·BioMed Research International·Can-Jie GuoXiong Ma
Mar 22, 2016·Journal of Clinical Medicine·Mio Kitano, P Mark Bloomston
Mar 19, 2019·Oxidative Medicine and Cellular Longevity·Shashank ShrishrimalRebecca E Oberley-Deegan

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