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Abstract：
Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs expressed in ATII cells might contribute to the regulation of signaling pathways. We purified \"untouched by antibodies\" ATII cells using a flow cytometric sorting method with a highly autofluorescent population of lung cells. TaqMan® miRNA low-density arrays were performed on sorted cells and intersected with miRNA profiles of ATII cells isolated according to a previously published protocol. Of 293 miRNAs expressed in both ATII preparations, 111 showed equal abundances. The target mRNAs of bona fide ATII miRNAs were used for pathway enrichment analysis. This analysis identified nine signaling pathways with known functions in fibrosis and/or epithelial-to-mesenchymal transition (EMT). In particular, a subset of 19 miRNAs was found to target 21 components of the TGF-β signaling pathway. Three of these miRNAs (miR-16-5p, -17-5p and -30c-5p) were down-modulated by TGF-β1 stimulation in human A549 cells, and concomitant up-regulation of associated mRNA targets (BMPR2, JUN, RUNX2) was observed. These results suggest an important role for miRNAs in maintaining the homeostasis of the TGF-β signaling pathway in ATII cells under physiological conditions.
摘要：
肺泡II型（ATII）细胞对于维持肺泡稳态至关重要。然而,miRNAs和miRNA调节网络的表达的知识是有限的,它们控制小鼠ATII细胞的稳态和协调多种功能。因此,我们询问在ATII细胞中表达的miRNAs如何促进信号通路的调节。我们使用具有高度自身荧光的肺细胞群的流式细胞术分选方法纯化了“未被抗体触及”的ATII细胞。在分选的细胞上进行TaqMan®miRNA低密度阵列,并与根据先前公布的方案分离的ATII细胞的miRNA谱相交。在两种ATII制剂中表达的293种miRNA中，111显示出相等的丰度。真正的ATIImiRNA的靶mRNA用于途径富集分析。该分析鉴定了在纤维化和/或上皮-间质转化(EMT)中具有已知功能的9个信号传导途径。特别是,我们发现19个miRNA的一个子集靶向TGF-β信号通路的21个组分.这些miRNA中的三个（miR-16-5p，-17-5p和-30c-5p）在人A549细胞中被TGF-β1刺激下调，并伴随相关mRNA靶标的上调(BMPR2，JUN，观察到RUNX2）。这些结果表明miRNAs在维持ATII细胞中TGF-β信号通路在生理条件下的稳态中的重要作用。
