miRNA-200c mediates mono-butyl phthalate-disrupted steroidogenesis by targeting vimentin in Leydig tumor cells and murine adrenocortical tumor cells
miRNA-200c mediates mono-butyl phthalate-disrupted steroidogenesis by targeting vimentin in Leydig tumor cells and murine adrenocortical tumor cells
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miRNA-200c 通过靶向 Leydig 肿瘤细胞和鼠肾上腺皮质肿瘤细胞中的波形蛋白来介导邻苯二甲酸单丁酯破坏的类固醇生成
DOI：
10.1016/j.toxlet.2015.11.009
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发表时间：
2016-01-22
影响因子：
3.5
通讯作者：
Wang, Yubang
中科院分区：
文献类型：
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作者：
Lu, Hongchao;Zhang, Chang;Wang, Yubang
增塑剂邻苯二甲酸二正丁酯（DBP）及其活性代谢物邻苯二甲酸单丁酯（MBP）已在啮齿动物中证明了生殖毒性。本研究旨在探讨波形蛋白（vimentin）和miRNA-200 c在MBP干预类固醇合成中的作用。采用小鼠Leydig肿瘤细胞（MLTC-1）和小鼠肾上腺皮质肿瘤细胞（Y1），并暴露于不同水平的MBP（10（-7）、10（-6）、10（-5）和10（-4）M）。当MLTC-1和Y1细胞暴露于10（-7）M的MBP时，类固醇激素的产生显著增加。此外，波形蛋白和类固醇生成急性调节蛋白（星星）的表达上调，在相同的剂量。发现MBP通过促进波形蛋白介导的胆固醇转移过程而增加类固醇生成。相比之下，两种细胞中的miRNA-200 c表达在MBP剂量（10（-7）M）下均受到抑制。此外，波形蛋白的表达和孕酮的生产增加MLTC-1和Y1细胞后，miRNA-200 c的表达被人为抑制。这些结果强烈表明MBP通过miRNA-200 c上调波形蛋白来提高类固醇激素的合成。(C)2015爱思唯尔爱尔兰有限公司版权所有。
The reproductive toxicity of plasticizer di-n-butyl phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) has been demonstrated in rodents. The objective of this study was to explore roles of vimentin and miRNA-200c in steroidogenesis interfered by MBP. Mouse Leydig tumor cells (MLTC-1) and murine adrenocortical tumor cells (Y1) were employed and exposed to various levels of MBP (10(-7), 10(-6), 10(-5) and 10(-4) M). Steroid hormone production was increased significantly when MLTC-1 and Y1 cells were exposed to MBP at 10(-7) M. Additionally, vimentin and steroidogenic acute regulatory protein (StAR) expressions were upregulated at the same dose. It was found that MBP increased the steroidogenesis by facilitating the cholesterol transfer process by vimentin. In contrast, miRNA-200c expression was depressed at doses of MBP (10(-7) M) in both cells. Moreover, vimentin expression and progesterone production were increased in both MLTC-1 and Y1 cells after miRNA-200c expression was artificially inhibited. These results strongly suggested that MBP raised steroid hormone synthesis via upregulated vimentin by miRNA-200c. (C) 2015 Elsevier Ireland Ltd. All rights reserved.