Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands.
Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands.
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DOI：
10.1371/journal.pone.0065127
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Taya K
中科院分区：
文献类型：
--
作者：
Nagaoka K;Zhang H;Watanabe G;Taya K
乳腺上皮细胞经历增殖、分化和退化的周期性循环。许多研究表明，miRNAs是一种小的非编码RNA，在转录后调控过程中影响多种生物学过程。在这里，我们发现一种miRNA，miR-200 a，在小鼠的乳腺、肺和肾脏等富含上皮细胞的器官中表达相对较高。在乳腺中，miR-200 a的表达在妊娠中期至哺乳期间增加;其表达受到乳腺上皮细胞的催乳激素处理的刺激。泌乳素还诱导乳蛋白β-酪蛋白mRNA（细胞分化的标志物）和E-钙粘蛋白mRNA（上皮细胞的标志物）的表达。然而，miR-200 a的敲低阻止了β-酪蛋白和E-钙粘蛋白mRNA表达的增加。蛋白质分析显示，在miR-200 a敲低后，E-cadherin信号降低，ZEB 1（EMT的标志物）增加。最后，在模拟含管腔乳腺导管的三维培养系统中，miR-200 a敲低降低了空腔形成率并抑制了claudin-3和par-6 b表达，表明上皮细胞极性降低。这些观察结果表明，miR-200 a对于维持上皮细胞表型是重要的，这有助于催乳激素诱导乳腺中的细胞分化。
Mammary gland epithelial cells undergo periodic cycles of proliferation, differentiation, and involution. Many studies have reported that miRNAs, which are small, non-coding RNAs, influence a variety of biological processes during posttranscriptional regulation. Here, we found that one miRNA, miR-200a, was relatively highly expressed in epithelial cell-rich organs such as mammary glands, lung, and kidney in mice. In mammary glands, miR-200a expression increased during mid-pregnancy through lactation; its expression was stimulated by lactogenic hormone treatment of mammary epithelial cells. Lactogenic hormone also induced the expression of milk protein ß-casein mRNA (a marker of cell differentiation) and E-cadherin mRNA (a marker of epithelial cells). However, knockdown of miR-200a prevented increases in ß-casein and E-cadherin mRNA expression. Protein analysis revealed that E-cadherin signal was decreased and ZEB1 (a marker of EMT) was increased following miR-200a knockdown. Finally, in a three-dimensional culture system modeling lumen-containing mammary ducts, miR-200a knockdown decreased the cavity formation rate and suppressed claudin-3 and par-6b expression, indicating reduced epithelial cell polarity. These observations suggest that miR-200a is important for maintaining the epithelial cell phenotype, which contributes to lactogenic hormone induction of cellular differentiation in mammary glands.
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影响因子：
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作者：
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通讯作者：
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