PMID- 31638173
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20200413
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 44
IP  - 6
DP  - 2019 Dec
TI  - 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.
PG  - 2201-2212
LID - 10.3892/ijmm.2019.4375 [doi]
AB  - 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‑3beta (GSK3beta), 
      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 1alpha (CPT1alpha) and 
      adenosine 5‑monophosphate (AMP)‑activated protein kinase alpha (AMPKalpha), 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/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.
FAU - Wang, Xiu-Mei
AU  - Wang XM
AD  - Department of Gastroenterology, The First People's Hospital of Neijiang, 
      Neijiang, Sichuan 641000, P.R. China.
FAU - Wang, Xiao-Yi
AU  - Wang XY
AD  - Department of Gastroenterology, The Second People's Hospital of Yibin, Yibin, 
      Sichuan 644000, P.R. China.
FAU - Huang, Yu-Mei
AU  - Huang YM
AD  - Department of Gastroenterology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan 646000, P.R. China.
FAU - Chen, Xia
AU  - Chen X
AD  - Department of Gastroenterology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan 646000, P.R. China.
FAU - Lu, Mu-Han
AU  - Lu MH
AD  - Department of Gastroenterology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan 646000, P.R. China.
FAU - Shi, Lei
AU  - Shi L
AD  - Department of Gastroenterology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan 646000, P.R. China.
FAU - Li, Chang-Ping
AU  - Li CP
AD  - Department of Gastroenterology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan 646000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20191018
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Antagomirs)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-6)
RN  - 0 (Lrp6 protein, mouse)
RN  - 0 (MIRN21 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (beta Catenin)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Animals
MH  - Antagomirs/genetics/pharmacology
MH  - Choline/metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/genetics
MH  - Glycogen Synthase Kinase 3 beta/genetics
MH  - Humans
MH  - Low Density Lipoprotein Receptor-Related Protein-6/*genetics
MH  - Methionine/metabolism
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Non-alcoholic Fatty Liver Disease/*genetics/metabolism
MH  - Wnt Signaling Pathway/*genetics
MH  - beta Catenin/genetics
PMC - PMC6844630
EDAT- 2019/10/23 06:00
MHDA- 2020/04/14 06:00
PMCR- 2019/10/18
CRDT- 2019/10/23 06:00
PHST- 2019/04/14 00:00 [received]
PHST- 2019/10/01 00:00 [accepted]
PHST- 2019/10/23 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2019/10/23 06:00 [entrez]
PHST- 2019/10/18 00:00 [pmc-release]
AID - ijmm-44-06-2201 [pii]
AID - 10.3892/ijmm.2019.4375 [doi]
PST - ppublish
SO  - Int J Mol Med. 2019 Dec;44(6):2201-2212. doi: 10.3892/ijmm.2019.4375. Epub 2019 
      Oct 18.