Regulation of cyclin D1 by arsenic and microRNA inhibits adipogenesis.
Regulation of cyclin D1 by arsenic and microRNA inhibits adipogenesis.
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DOI：
10.1016/j.toxlet.2016.12.002
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发表时间：
2017-01-04
影响因子：
3.5
通讯作者：
Barchowsky, Aaron
中科院分区：
文献类型：
--
作者：
Beezhold, Kevin;Klei, Linda R.;Barchowsky, Aaron
低剂量长期暴露于饮用水中的砷是一个全球公共卫生问题，具有代谢和心血管疾病以及癌症的既定风险。虽然砷和疾病之间的联系很强，但需要进一步了解其致病性的分子机制。先前的报道表明砷能够干扰脂肪形成，这可能介导其促进代谢疾病的作用。我们假设microRNA是大多数（如果不是所有）间充质干细胞过程的重要调节因子，这些过程因砷暴露而失调，从而损害脂肪生成。砷增加了白色脂肪组织中miR-29 b的表达，以及从脂肪组织中分离的人间充质干细胞（hMSC）。暴露于砷的hMSCs增加了miR-29 b和细胞周期蛋白D1的丰度，以促进增殖超过分化。有趣的是，miR-29 b的抑制增强了砷对分化的抑制作用。这种矛盾归因于miR-29在调节细胞周期蛋白D1表达中的需要，因为稳定抑制miR-29 b消除了细胞周期蛋白D1表达的循环模式。细胞周期蛋白D1的时间调节对于脂肪形成分化至关重要，并且数据表明砷破坏miR-29 b调节途径损害脂肪形成分化并最终损害脂肪代谢稳态的范例。
Low-dose chronic exposure to arsenic in drinking water represents a global public health concern with established risks for metabolic and cardiovascular disease, as well as cancer. While the linkage between arsenic and disease is strong, further understanding of the molecular mechanisms of its pathogenicity is required. Previous reports demonstrated the ability of arsenic to interfere with adipogenesis, which may mediate its effects in promoting metabolic disease. We hypothesized that microRNA are important regulators of most if not all mesenchymal stem cell processes that are dysregulated by arsenic exposure to impair lipogenesis. Arsenic increased the expression of miR-29b in white adipose tissue, as well as human mesenchymal stem cells (hMSCs) isolated from adipose tissue. Exposing hMSCs to arsenic increased abundance of miR-29b and cyclin D1 to promote proliferation over differentiation. Paradoxically, inhibition of miR-29b enhanced the inhibitory effect of arsenic on differentiation. This paradox was attributed to a requirement for miR-29 in regulating cyclin D1 expression as stable inhibition of miR-29b eliminated the cyclic pattern of cyclin D1 expression. Temporal regulation of cyclin D1 is critical for adipogenic differentiation, and the data suggest a paradigm where arsenic disruption of miR-29b regulatory pathways impairs adipogenic differentiation and ultimately adipose metabolic homeostasis.
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影响因子：
7.4
作者：
Ambrosio, Fabrisia;Brown, Elke;Stolz, Donna;Ferrari, Ricardo;Goodpaster, Bret;Deasy, Bridget;Distefano, Giovanna;Roperti, Alexandra;Cheikhi, Amin;Garciafigueroa, Yesica;Barchowsky, Aaron
通讯作者：
Barchowsky, Aaron
影响因子：
3.8
作者：
Beezhold, Kevin;Liu, Jia;Chen, Fei
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Chen, Fei
影响因子：
3.7
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Andersen, Ditte C.;Jensen, Charlotte H.;Sheikh, Soren P.
通讯作者：
Sheikh, Soren P.
影响因子：
4.8
作者：
Fu, MF;Rao, M;Pestell, RG
通讯作者：
Pestell, RG
影响因子：
3.8
作者：
Hughes, Michael F.;Beck, Barbara D.;Thomas, David J.
通讯作者：
Thomas, David J.