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Publication : 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.

First Author  Wang XM Year  2019
Journal  Int J Mol Med Volume  44
Issue  6 Pages  2201-2212
PubMed ID  31638173 Mgi Jnum  J:290845
Mgi Id  MGI:6435434 Doi  10.3892/ijmm.2019.4375
Citation  Wang XM, et al. (2019) Role and mechanisms of action of microRNA21 as regards the regulation of the WNT/betacatenin signaling pathway in the pathogenesis of nonalcoholic fatty liver disease. Int J Mol Med 44(6):2201-2212
abstractText  The aim of the present study was to investigate the role of microRNA21 (miR21) in regulating the classical WNT/betacatenin signaling pathway by targeting lowdensity lipoproteinrelated receptor 6 (LRP6) in nonalcoholic fatty liver disease (NAFLD). For this purpose, we established a NAFLD model by feeding C57BL/6J mice a methioninecholinedeficient diet. Antagomir21 was then injected via the tail vein, and the expression levels of WNT/betacatenin signaling pathwayrelated proteins, such as LRP6, glycogen synthase kinase3beta (GSK3beta), pbetacatenin, betacatenin and the downstream protein, peroxisome proliferatoractivated receptor gamma (PPARgamma), and lipid metabolismrelated genes, including sterol regulatory elementbinding transcription factor 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyl transferase 1alpha (CPT1alpha) and adenosine 5monophosphate (AMP)activated protein kinase alpha (AMPKalpha), were detected. The results revealed that in the NAFLD model, LRP6 expression was negatively associated with miR21 expression. After antagonizing the expression of miR21, the protein level of LRP6 was increased. In addition, the WNT/betacatenin signaling pathway was activated, and lipid accumulation and inflammation were alleviated in the liver. However, the expression of PPARgamma was not inhibited following the upregulation of the WNT signaling pathway. Taken together, the results of this study demonstrate that the inhibition of miR21 expression can alleviate NAFLD by targeting LRP6 to activate the WNT/betacatenin signaling pathway.
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