MiR-21a-5p suppresses bisphenol A-induced pre-adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK.
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.
['Xie|Xiuwen|X|', 'Song|Jia|J|', 'Li|Gang|G|']
D020413:3' Untranslated Regions D041721:3T3-L1 Cells D017667:Adipocytes D052242:Adiponectin D000818:Animals D001559:Benzhydryl Compounds D001835:Body Weight D002454:Cell Differentiation D005786:Gene Expression Regulation D008055:Lipids D048371:MAP Kinase Kinase 3 D051379:Mice D035683:MicroRNAs D010014:Osteolysis D010636:Phenols D010766:Phosphorylation D051381:Rats D017207:Rats, Sprague-Dawley D015398:Signal Transduction D014162:Transfection D048051:p38 Mitogen-Activated Protein Kinases
miR-21a-5p Differentiation map2k3 MKK3/p38/MAPK Obesity