Long Non-Coding RNAs Involved in Progression of Non-Alcoholic Fatty Liver Disease to Steatohepatitis
| Autor: | Bart van de Sluis, Folkert Kuipers, Ronit Shiri-Sverdlov, Cisca Wijmenga, Jingyuan Fu, Glenn Marsman, Biljana Atanasovska, Sander S. Rensen, Sebo Withoff |
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| Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Surgery, RS: NUTRIM - R2 - Liver and digestive health, Moleculaire Genetica |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cirrhosis PATHOGENESIS Non-alcoholic Fatty Liver Disease/genetics LIPOTOXICITY Fatty Acids Nonesterified Chronic liver disease Transcriptome long non-coding RNAs Fatty Acids Nonesterified/pharmacology Long Noncoding/genetics ENDOPLASMIC-RETICULUM STRESS Liver/drug effects RNA-Seq Biology (General) Fatty Acids NF-kappa B/genetics Fatty liver NF-kappa B Hep G2 Cells General Medicine 3. Good health Liver Tumor Necrosis Factor-alpha/pharmacology Disease Progression RNA Long Noncoding Tumor necrosis factor alpha Inflammation Mediators Hepatocytes/drug effects Liver cancer functional genomics HEPATIC INFLAMMATION QH301-705.5 PATHOPHYSIOLOGY KAPPA-B Biology Article MECHANISMS 03 medical and health sciences medicine Humans Gene silencing RNA Long Noncoding/genetics RECEPTOR 030102 biochemistry & molecular biology Tumor Necrosis Factor-alpha Gene Expression Profiling non-alcoholic fatty liver disease medicine.disease digestive system diseases 030104 developmental biology Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Case-Control Studies Nonesterified/pharmacology Hepatocytes Cancer research RNA Steatohepatitis |
| Zdroj: | Cells, 10, 8 Cells Cells, Vol 10, Iss 1883, p 1883 (2021) Volume 10 Issue 8 Cells, 10 Cells, 10(8):1883, 1-15. MDPI AG Cells, 10(8):1883. Multidisciplinary Digital Publishing Institute (MDPI) |
| ISSN: | 2073-4409 |
| Popis: | Contains fulltext : 238435.pdf (Publisher’s version ) (Open Access) Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is characterized by different stages varying from benign fat accumulation to non-alcoholic steatohepatitis (NASH) that may progress to cirrhosis and liver cancer. In recent years, a regulatory role of long non-coding RNAs (lncRNAs) in NAFLD has emerged. Therefore, we aimed to characterize the still poorly understood lncRNA contribution to disease progression. Transcriptome analysis in 60 human liver samples with various degrees of NAFLD/NASH was combined with a functional genomics experiment in an in vitro model where we exposed HepG2 cells to free fatty acids (FFA) to induce steatosis, then stimulated them with tumor necrosis factor alpha (TNFα) to mimic inflammation. Bioinformatics analyses provided a functional prediction of novel lncRNAs. We further functionally characterized the involvement of one novel lncRNA in the nuclear-factor-kappa B (NF-κB) signaling pathway by its silencing in Hepatoma G2 (HepG2) cells. We identified 730 protein-coding genes and 18 lncRNAs that responded to FFA/TNFα and associated with human NASH phenotypes with consistent effect direction, with most being linked to inflammation. One novel intergenic lncRNA, designated lncTNF, was 20-fold up-regulated upon TNFα stimulation in HepG2 cells and positively correlated with lobular inflammation in human liver samples. Silencing lncTNF in HepG2 cells reduced NF-κB activity and suppressed expression of the NF-κB target genes A20 and NFKBIA. The lncTNF we identified in the NF-κB signaling pathway may represent a novel target for controlling liver inflammation. |
| Databáze: | OpenAIRE |
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