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

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

Author information

1
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China. Electronic address: xiuwen_xie127@163.com.
2
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.

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

PMID:
26996129
DOI:
10.1016/j.bbrc.2016.03.066
[Indexed for MEDLINE]

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