Role And Mechanisms Of Action Of Microrna-21 As Regards The Regulation Of The Wnt/Beta-Catenin Signaling Pathway In The Pathogenesis Of Non-Alcoholic Fatty Liver Disease

The aim of the present study was to investigate the role of microRNA-21 (miR-21) in regulating the classical WNT/beta-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/beta-catenin signaling pathway-related proteins, such as LRP6, glycogen synthase kinase-3 beta (GSK3 beta), p-beta-catenin, beta-catenin and the downstream protein, peroxisome proliferator-activated receptor gamma (PPAR-gamma), and lipid metabolism-related genes, including sterol regulatory element-binding transcription factor 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyl transferase 1 alpha (CPT1 alpha) and adenosine 5-monophosphate (AMP)-activated protein kinase alpha (AMPK alpha), 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/beta-catenin signaling pathway was activated, and lipid accumulation and inflammation were alleviated in the liver. However, the expression of PPAR-gamma 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/beta-catenin signaling pathway.