Role and mechanisms of action of microRNA-21 as regards the regulation of the WNT/β-catenin signaling pathway in the pathogenesis of non-alcoholic fatty liver disease
| Autor: | Xiu‑Mei Wang, Lei Shi, Chang‑Ping Li, Xiao‑Yi Wang, Mu‑Han Lü, Yu‑Mei Huang, Xia Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
LRP6 Choline 03 medical and health sciences Mice 0302 clinical medicine Methionine Downregulation and upregulation Genetics Animals Humans Protein kinase A Transcription factor Wnt Signaling Pathway beta Catenin Glycogen Synthase Kinase 3 beta Oncogene biology Chemistry Wnt signaling pathway non-alcoholic fatty liver disease Antagomirs General Medicine Articles WNT/β-catenin signaling pathway Cell biology Fatty acid synthase Disease Models Animal MicroRNAs 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Low Density Lipoprotein Receptor-Related Protein-6 biology.protein Signal transduction microRNA-21 |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | The aim of the present study was to investigate the role of microRNA-21 (miR-21) in regulating the classical WNT/β-catenin signaling pathway by targeting low-density lipoprotein-related receptor 6 (LRP6) in non-alcoholic fatty liver disease (NAFLD). For this purpose, we established a NAFLD model by feeding C57BL/6J mice a methionine-choline-deficient diet. Antagomir-21 was then injected via the tail vein, and the expression levels of WNT/β-catenin signaling pathway-related proteins, such as LRP6, glycogen synthase kinase-3β (GSK3β), p-β-catenin, β-catenin and the downstream protein, peroxisome proliferator-activated receptor γ (PPAR-γ), and lipid metabolism-related genes, including sterol regulatory element-binding transcription factor 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyl transferase 1α (CPT1α) and adenosine 5-monophosphate (AMP)-activated protein kinase α (AMPKα), were detected. The results revealed that in the NAFLD model, LRP6 expression was negatively associated with miR-21 expression. After antago-nizing the expression of miR-21, the protein level of LRP6 was increased. In addition, the WNT/β-catenin signaling pathway was activated, and lipid accumulation and inflammation were alleviated in the liver. However, the expression of PPAR-γ was not inhibited following the upregulation of the WNT signaling pathway. Taken together, the results of this study demonstrate that the inhibition of miR-21 expression can alleviate NAFLD by targeting LRP6 to activate the WNT/β-catenin signaling pathway. |
| Databáze: | OpenAIRE |
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