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- W3136144893 abstract "Abstract Background Non-alcoholic steatohepatitis (NASH) is a key stage in leading development of non-alcoholic simple fatty liver (NAFL) into cirrhosis and even liver cancer. This study aimed at exploring the lncRNAs expression profile in NASH and the biological function of a novel LncRNA-gm9795. Methods Microarray analysis was performed to compare the expression profiles of lncRNAs in the liver of NASH, NAFLD and normal mice (5 mice for each group). Methionine-choline-deficient Medium (MCD) with Lipopolysaccharide (LPS) or palmitic acid (PA)were used to built NASH cell models. The role and mechanism of LncRNA-gm9795 in NASH were explored by knocking down or over-expressing its expression. Results A total of 381 lncRNAs were found to be not only highly expressed in NAFLD, but also is going to go even higher in NASH. A novel LncRNA-gm9795 was significantly highly expressed in liver tissues of NASH animal models and NASH cell models. By staining with Nile red, we found that gm9795 did not affect the fat accumulation of NASH. However, gm9795 in NASH cell models significantly promoted the expression of TNF $$alpha {}$$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML> <mml:mrow> <mml:mi>α</mml:mi> <mml:mrow /> </mml:mrow> </mml:math> , IL-6, IL-1 $$beta {}$$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML> <mml:mrow> <mml:mi>β</mml:mi> <mml:mrow /> </mml:mrow> </mml:math> , the important inflammatory mediators in NASH. At the same time, we found that gm9795 upregulated the key molecules in endoplasmic reticulum stress (ERS), while NF- $$kappa {}$$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML> <mml:mrow> <mml:mi>κ</mml:mi> <mml:mrow /> </mml:mrow> </mml:math> B/JNK pathways were also activated. When ERS activator Thapsigargin (TG) was introduced in cells with Ggm9757 si-RNA, NF- $$kappa {}$$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML> <mml:mrow> <mml:mi>κ</mml:mi> <mml:mrow /> </mml:mrow> </mml:math> B and JNK pathways were activated. Conversely, ERS inhibitor Tauroursodeoxycholic acid (TUDCA) inhibited NF-kB and JNK pathways in cells with gm9795 overexpression plasmid. Conclusion LncRNA-gm9795 promotes inflammatory response in NASH through NF-kB and JNK pathways by ERS, which might provide theoretical basis for revealing the pathogenesis of NASH and discovering new therapeutic targets" @default.
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- W3136144893 date "2021-03-09" @default.
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- W3136144893 title "LncRNA-Gm9795 promotes inflammation in non-alcoholic steatohepatitis via NF-$$kappa {}$$B/JNK pathway by endoplasmic reticulum stress" @default.
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- W3136144893 doi "https://doi.org/10.1186/s12967-021-02769-7" @default.
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