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 $$\alpha {}$$ α , IL-6, IL-1$$\beta {}$$ β , 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-$$\kappa {}$$ κ B/JNK pathways were also activated. When ERS activator Thapsigargin (TG) was introduced in cells with Ggm9757 si-RNA, NF-$$\kappa {}$$ κ 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

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 lncRNA expression profifile in NASH and the biological function of a novel LncRNA-gm9795. Methods: Microarray analysis was performed to compare the expression profifiles of lncRNAs in the liver of NASH, NAFLD and normal mice. 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 TNFα, IL-6, IL-1β, 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-κB/JNK pathways were also activated. When ERS activator Thapsigargin(TG) was introduced in cells with Gm9757 si-RNA, NF-κB and JNK pathways were activated. Conversely, ERS inhibitor Tauroursodeoxycholic(TUDCA) acid 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

Background The genetic mechanism of glucose metabolism has not been elucidated in nonalcoholic steatohepatitis (NASH), and many genes are took part in glucose metabolism of NASH. In this study, we used the weighted gene co-expression network analysis (WGCNA) to find the key genes associated with glucose metabolism; Methods Data sets GSE96971 and GSE89632 from Gene Expression Omnibus (GEO) were analyzed by WGCNA. We screened the Hub gene from the GSE96971 dataset, and the selected Hub genes were verified by GSE89632 dataset. We then analyzed the dataset using the Gene Ontology (GO) term enrichment and the Kyoto Encyclopedia of Genome (KEGG) path analysis. Expression levels of the hub genes are assessed by qPCR analysis. The function of hub genes was verified by Nile Red staining and relative glucose consumption detection; Results The hub genes are mannosidase beta like (MANBAL), myc proto-oncogene protein (MYC), caspase 4 (CASP4), CDK5 regulatory subunit associated protein 3 (CDK5RAP3) and ZFP36 ring finger protein (ZFP36) in the datasets GSE96971 and the GSE89632. Further, these genes are mainly involved in the integral component of membrane and plasma membrane, the PI3K-AKT signaling pathway and the olfactory transduction according to the GO and KEGG results. These hub genes were significantly up-regulated in the palmitic acid (PA) cell model and methionine-choline-deficient medium (MCD) cell model. After knocking out the hub genes in PA model and the MCD model of NASH, relative glucose consumption was increased and lipid deposition was reduced compared with the control group; Conclusions MANBAL, MYC, CASP4, CDK5RAP3 and ZFP36 are elevated and involved in the pathogenesis of NASH. Further research on these genes are warranted.