University of Giessen Lung Center, Excellence Cluster in Cardio-Pulmonary Systems, member of the German Lung Center (DZL), Department of Internal Medicine II, Aulweg 130, 35392 Giessen, Germany.
Development. 2014 Mar;141(6):1272-81. doi: 10.1242/dev.105908. Epub 2014 Feb 19.
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 β-catenin-mediated WNT signaling.
肺间质中增殖和分化之间的平衡调控在很大程度上还没有得到充分描述，不像其上皮对应物那样。在这项研究中，我们确定 miR-142-3p 通过控制 WNT 信号水平，有助于间质祖细胞的适当增殖。miR-142-3p 可以与腺瘤性结肠息肉病 mRNA 物理结合，从而调节其表达水平。在 miR-142-3p 功能丧失实验中，副支气管平滑肌细胞祖细胞的增殖明显受损，导致过早分化。WNT 信号在间质中的激活，或 APC 功能丧失，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 信号水平，在 FGFR2C 和β-连环蛋白介导的 WNT 信号反馈环之间增加了一层额外的控制。
