miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development
miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development
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DOI：
10.1242/dev.105908
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发表时间：
2014-03-15
期刊：
影响因子：
4.6
通讯作者：
Bellusci, Saverio
中科院分区：
文献类型：
--
作者：
Carraro, Gianni;Shrestha, Amit;Bellusci, Saverio
与肺上皮细胞不同，肺间质间室中增殖和分化平衡的调节在很大程度上是未知的。在这项研究中，我们确定miR-142-3p通过控制WNT信号水平来促进间充质祖细胞的适当增殖。miR-142-3p可以物理结合大肠腺瘤性息肉病mRNA，调节其表达水平。在miR-142-3p功能缺失实验中，支气管旁平滑肌细胞祖细胞的增殖明显受损，导致过早分化。间质中WNT信号的激活或Apc功能的丧失都可以挽救miR-142-3p的敲低。这些发现表明，在胚胎肺间质中，microRNA机制调节WNT信号传导水平，在FGFR2C和β -连环蛋白介导的WNT信号传导之间的反馈回路中增加了一层额外的控制。
The regulation of the balance between proliferation and differentiation in the mesenchymal compartment of the lung is largely uncharacterized, unlike its epithelial counterpart. In this study, we determined that miR-142-3p contributes to the proper proliferation of mesenchymal progenitors by controlling the level of WNT signaling. miR-142-3p can physically bind to adenomatous polyposis coli mRNA, functioning to regulate its expression level. In miR-142-3p loss-of-function experiments, proliferation of parabronchial smooth muscle cell progenitors is significantly impaired, leading to premature differentiation. Activation of WNT signaling in the mesenchyme, or Apc loss of function, can both rescue miR-142-3p knockdown. These findings show that in the embryonic lung mesenchyme, the microRNA machinery modulates the level of WNT signaling, adding an extra layer of control in the feedback loop between FGFR2C and beta-cateninmediated WNT signaling.