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

• Published in: International journal of molecular medicine Vol. 44; no. 6; pp. 2201 - 2212
• Main Authors: Wang, Xiu-Mei, Wang, Xiao-Yi, Huang, Yu-Mei, Chen, Xia, Lü, Mu-Han, Shi, Lei, Li, Chang-Ping
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.12.2019; D.A. Spandidos
• Subjects: Animals; Antagomirs - genetics; Antagomirs - pharmacology; beta Catenin - genetics; Choline - metabolism; Dehydrogenases; Disease Models, Animal; Drug dosages; Fatty acids; Feeds; Gene expression; Gene Expression Regulation - genetics; Glycogen Synthase Kinase 3 beta - genetics; Humans; Immunoglobulins; Inflammation; Kinases; Laboratory animals; Lipids; Liver diseases; Low Density Lipoprotein Receptor-Related Protein-6 - genetics; Metabolism; Methionine - metabolism; Mice; MicroRNAs; MicroRNAs - genetics; NMR; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - metabolism; Nuclear magnetic resonance; Pathogenesis; Proteins; Sterols; Transcription factors; Wnt Signaling Pathway - genetics
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2019.4375

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 antagonizing 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.