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

Wang,Xiu‑Mei; Wang,Xiao‑Yi; Huang,Yu‑Mei; Chen,Xia; Lü,Mu‑Han; Shi,Lei; Li,Chang‑Ping

doi:10.3892/ijmm.2019.4375

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

Authors:
- Xiu‑Mei Wang
- Xiao‑Yi Wang
- Yu‑Mei Huang
- Xia Chen
- Mu‑Han Lü
- Lei Shi
- Chang‑Ping Li
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Affiliations: Department of Gastroenterology, The First People's Hospital of Neijiang, Neijiang, Sichuan 641000, P.R. China, Department of Gastroenterology, The Second People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: October 18, 2019 https://doi.org/10.3892/ijmm.2019.4375
Pages: 2201-2212
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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