Benzyl butyl phthalate induces epigenetic stress to enhance adipogenesis in mesenchymal stem cells.
Mol Cell Endocrinol
; 431: 109-22, 2016 08 15.
Article
em En
| MEDLINE
| ID: mdl-27164441
ABSTRACT
Endocrine disruptors, phthalates, may have contributed to recent global obesity health crisis. Our study investigated the potential of benzyl butyl phthalate (BBP) to regulate the mesenchymal stem cell epigenome to drive adipogenesis. BBP exposure enhanced lipid accumulation and adipogenesis in a dose-dependent manner compared to control (P < 0.001). Adipogenesis markers, PPARγ (P < 0.001), C/EBPα (P < 0.01), and aP2 (P < 0.001) were significantly upregulated by increasing concentrations of BBP when compared to DMSO. BBP enhanced H3K9 acetylation while decreasing H3K9 dimethylation. Fifty µM BBP increased histone acetyltransferases, p300 (P < 0.05) and GCN5 (P < 0.01) gene expression. Furthermore, histone deacetylases (HDACs), HDAC3 (P < 0.01) and HDAC10 (P < 0.01, 10 µM BBP; P < 0.001, 50 µM BBP) and histone methyltransferases, SETDB1 (P < 0.01) and G9a (P < 0.01), were significantly downregulated by BBP exposure. BBP acts, in part, through PPARγ, as PPARγ knockdown led to decreased H3K9ac and rescued H3K9me2 during BBP exposure. In conclusion, BBP regulated MSCs towards adipogenesis by tipping the epigenomic balance.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Ftálicos
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Epigênese Genética
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Adipogenia
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Células-Tronco Mesenquimais
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Endocrinol
Ano de publicação:
2016
Tipo de documento:
Article