Knockout of microRNA-21 attenuates alcoholic hepatitis through the VHL/NF-κB signaling pathway in hepatic stellate cells

American Journal of Physiology. Gastrointestinal and Liver Physiology
Nan WuFanyin Meng

Abstract

microRNA-21 (miRNA) is one of the most abundant miRNAs in chronic liver injuries including alcoholic liver injury. Previous studies have demonstrated that miR-21 plays a role in inflammation in the liver and functions in hepatic stellate cells (HSCs), which reside in the perisinusoidal space between sinusoidal endothelial cells and hepatocytes and regulate sinusoidal circulation. HSCs integrate cytokine-mediated inflammatory responses in the sinusoids and relay them to the liver parenchyma. Here, we showed that the activation of Von Hippel-Lindau (VHL) expression, by miR-21 knockout in vivo and anti-miR-21 or VHL overexpression in vitro, suppressed the production of proinflammatory cytokines, such as interleukin (IL)-6, monocyte chemoattractant protein-1, and IL-1β, in human HSCs during alcoholic liver injury. Sequence and functional analyses confirmed that miR-21 directly targeted the 3'-untranslated region of VHL. Immunofluorescence and real-time PCR analysis revealed that miR-21 depletion blocked NF-κB activation in human HSCs both in cultured HSCs as well as HSCs isolated from alcohol-related liver disease mice liver by laser capture microdissection. We also showed that conditioned medium from anti-miR-21-transfected HSCs s...Continue Reading

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Citations

Sep 15, 2020·Nanotoxicology·Yiqun MoQunwei Zhang
Jan 3, 2019·Hepatology International·Beatriz Aguilar-Bravo, Pau Sancho-Bru
Sep 14, 2020·The American Journal of Pathology·Elise SlevinFanyin Meng

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Methods Mentioned

BETA
PCR
FCS
Transfections
laser capture microdissection
transfection
Infrared Imaging
ELISA
laser
nuclear translocation
nuclear

Software Mentioned

Olympus Image Pro - Analyzer
Ingenuity Pathway Analysis
SPSS
Volcano Plots
Ingenuity Pathway Analysis ( IPA )
TargetScan

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