title: MiR-21a-5p suppresses bisphenol A-induced pre-adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK.
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.
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China. Electronic address: xiuwen_xie127@163.com.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D041721:3T3-L1 Cells / Q000166:cytology; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000737:chemistry*; D001835:Body Weight; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D008055:Lipids / Q000097:blood; D048371:MAP Kinase Kinase 3 / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010014:Osteolysis / Q000378:metabolism; D010636:Phenols / Q000737:chemistry*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D020413:3' Untranslated Regions; D052242:Adiponectin; D001559:Benzhydryl Compounds; D008055:Lipids; D048371:MAP Kinase Kinase 3; D035683:MicroRNAs; D010636:Phenols; D048051:p38 Mitogen-Activated Protein Kinases; C531950:MIRN21 microRNA, mouse; C482531:Map2k3 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Differentiation; MKK3/p38/MAPK; Obesity; map2k3; miR-21a-5p