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http://purl.uniprot.org/citations/29106945http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Nonalcoholic fatty liver disease (NAFLD) is a common result of obesity and metabolic syndrome. Hepatocyte injury and metabolic disorders are hallmarks of NAFLD. Stimulator of interferon genes (STING) and its downstream factor interferon regulatory factor 3 (IRF3) trigger inflammatory reaction in response to the presence of cytosolic DNA. STING has recently been shown to play an important role in early alcoholic liver disease. However, little is known about the role of STING-IRF3 pathway in hepatocyte injury. Here, we aimed to examine the effect of STING-IRF3 pathway on hepatocyte metabolism, inflammation and apoptosis.

Methods

We examined the activation of the STING-IRF3 pathway, a high-fat diet (HFD)-induced obese mouse model, and determined the role of this pathway in a free fatty acid (FFA)-induced hepatocyte inflammatory response, injury, and dysfunction in L-O2 human liver cells.

Results

STING and IRF3 were upregulated in livers of HFD-fed mice and in FFA-induced L-O2 cells. Knocking down either STING or IRF3 led to a significant reduction in FFA-induced hepatic inflammation and apoptosis, as evidenced by modulation of the nuclear factor κB (NF-κB) signaling pathway, inflammatory cytokines, and apoptotic signaling. Additionally, STING/IRF3 knockdown enhanced glycogen storage and alleviated lipid accumulation, which were found to be associated with increased expression of hepatic enzymes in glycolysis and lipid catabolism, and attenuated expression of hepatic enzymes in gluconeogenesis and lipid synthesis.

Conclusions

Our results suggest that the STING-IRF3 pathway promotes hepatocyte injury and dysfunction by inducing inflammation and apoptosis and by disturbing glucose and lipid metabolism. This pathway may be a novel therapeutic target for preventing NAFLD development and progression."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.org/dc/terms/identifier"doi:10.1016/j.metabol.2017.09.010"xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Chen L."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Cui C."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Yan F."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Shen Y.H."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Wang L.S."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Liu F.Q."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Qing L."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Hou X.G."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"Qiao J.T."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/author"He T.Y."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/name"Metabolism"xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/pages"13-24"xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/title"Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease."xsd:string
http://purl.uniprot.org/citations/29106945http://purl.uniprot.org/core/volume"81"xsd:string
http://purl.uniprot.org/citations/29106945http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29106945
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