کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2195530 1550848 2016 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Benzyl butyl phthalate induces epigenetic stress to enhance adipogenesis in mesenchymal stem cells
ترجمه فارسی عنوان
بنزیل بوتیل فتالات باعث القای استرس اپی ژنتیک برای افزایش آلودگی زایی در سلول های بنیادی مزانشیمی می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی


• Benzyl butyl phthalate (BBP) enhances adipogenesis in mesenchymal stem cells
• BBP increases histone 3 lysine 9 acetylation by regulating HAT and HDAC expression
• BBP decreases histone 3 lysine 9 dimethylation and downregulates HMTs
• BBP epigenetically regulates mesenchymal stem cells towards adipogenesis

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 431, 15 August 2016, Pages 109–122
نویسندگان
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