MiR-21a-5p suppresses bisphenol A-induced pre-adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK

Biochem Biophys Res Commun. 2016 Apr 22;473(1):140-146. doi: 10.1016/j.bbrc.2016.03.066. Epub 2016 Mar 18.

Abstract

Childhood obesity is a metabolic disease characterized by accumulation of excessive fat. Bisphenol A (BPA), a potential obesogen compound, possesses an estrogen mimetic activity and endocrine disruption effect. MicroRNA-21a-5p (miR-21a-5p) is reported to regulate the adipogenic differentiation. Our study showed that miR-21a-5p overexpression significantly decreased the red lipid droplets and triglyceride level in BPA-induced 3T3-L1 cells. BPA induced the mRNA and protein expression levels of PPARγ, C/EBPα and adiponectin, and the induction was inhibited by miR-21a-5p mimics transfection. MiR-21a-5p mimics inhibited the GR activity, GR phosphorylation (S220, S21a-5p2, and S234), and the activation of p38/MAPK pathway, which are elevated by BPA treatment in 3T3-L1 cells. MiR-21a-5p overexpression inhibited the protein level of MKK3, but not in the mRNA level. Luciferase activity assay showed that miR-21a-5p directly targeted map2k3 3'-UTR. MKK3 overexpression attenuated the effect of miR-21a-5p mimics transfection on 3T3-L1 differentiation. We also assessed the body weight, fat mass and the content of serum lipid in rats subcutaneous injected with BPA and miR-21a-5p mimics. MiR-21a-5p overexpression attenuated BPA-induced obesity in vivo. These findings suggested that miR-21a-5p inhibited BPA induced adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK in 3T3-L1 cells, providing a potential therapeutic strategy for BPA induced obesity.

Keywords: Differentiation; MKK3/p38/MAPK; Obesity; map2k3; miR-21a-5p.

MeSH terms

  • 3' Untranslated Regions
  • 3T3-L1 Cells / cytology
  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adiponectin / metabolism
  • Animals
  • Benzhydryl Compounds / chemistry*
  • Body Weight
  • Cell Differentiation
  • Gene Expression Regulation*
  • Lipids / blood
  • MAP Kinase Kinase 3 / metabolism*
  • Mice
  • MicroRNAs / metabolism*
  • Osteolysis / metabolism
  • Phenols / chemistry*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transfection
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 3' Untranslated Regions
  • Adiponectin
  • Benzhydryl Compounds
  • Lipids
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Phenols
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 3
  • Map2k3 protein, mouse
  • bisphenol A