Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts
Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts
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DOI：
10.1152/ajplung.00149.2013
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发表时间：
2014-03-01
影响因子：
4.9
通讯作者：
Kaminski, Naftali
中科院分区：
文献类型：
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作者：
Huleihel, Luai;Ben-Yehudah, Ahmi;Kaminski, Naftali
MicroRNAs是抑制蛋白质表达的小的非编码rna。我们之前已经证明，在体外和体内，抑制上皮细胞中的microRNA let-7d会引起与上皮-间质转化（EMT）一致的变化。本研究的目的是确定将let-7d引入成纤维细胞是否会改变其间充质特性。用let-7d转染原代成纤维细胞导致间充质标志物α -平滑肌肌动蛋白、n-钙粘蛋白、成纤维细胞特异性蛋白-1和纤维连接蛋白的表达减少，上皮标志物紧密连接蛋白-1和角蛋白19的表达增加。表型变化也存在，包括伤口愈合延迟，运动性降低，转染后成纤维细胞增殖。此外，我们检测了转染对成纤维细胞对tgf - β的反应性的影响，tgf - β是许多纤维化过程（如肺纤维化）的重要因素，发现转染let-7d可显著减弱tgf - β诱导的高迁移率组- a2蛋白。我们的研究结果表明，上皮microRNA let-7d可以显著改变原代成纤维细胞的表型。
MicroRNAs are small noncoding RNAs that inhibit protein expression. We have previously shown that the inhibition of the microRNA let-7d in epithelial cells caused changes consistent with epithelial-to-mesenchymal transition (EMT) both in vitro and in vivo. The aim of this study was to determine whether the introduction of let-7d into fibroblasts alters their mesenchymal properties. Transfection of primary fibroblasts with let-7d caused a decrease in expression of the mesenchymal markers alpha-smooth muscle actin, N-cadherin, fibroblast-specific protein-1, and fibronectin, as well as an increase in the epithelial markers tight junction protein-1 and keratin 19. Phenotypic changes were also present, including a delay in wound healing, reduced motility, and proliferation of fibroblasts following transfection. In addition, we examined the effects of transfection on fibroblast responsiveness to TGF-beta, an important factor in many fibrotic processes such as lung fibrosis and found that let-7d transfection significantly attenuated high-mobility group-A2 protein induction by TGF-beta. Our results indicate that administration of the epithelial microRNA let-7d can significantly alter the phenotype of primary fibroblasts.