Chemokine expression in the early response to injury in human airway epithelial cells.
Chemokine expression in the early response to injury in human airway epithelial cells.
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DOI：
10.1371/journal.pone.0193334
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
White SR
中科院分区：
文献类型：
--
作者：
Xie B;Laxman B;Hashemifar S;Stern R;Gilliam TC;Maltsev N;White SR
基底气道上皮细胞(AEC)是中央呼吸道内的干/祖细胞，对黏膜损伤的反应按扩散、迁移、增殖和分化为所需细胞类型的顺序进行。然而，在黏膜损伤后的早期事件中，AEC中的动态基因转录尚未被研究。我们用基因芯片检测了机械损伤(MI)后原代人AEC在浸泡培养中产生基底细胞以及在气液界面产生分化的AEC(DAEC)，其中包括杯状细胞和纤毛细胞。在心肌梗死后2-24小时内，一组约150个基因在差异表达(DE)中，这些基因的富集性分析显示与炎症细胞因子和趋化因子相关的功能类别的过度表达。基于网络的基因优先排序和使用Pinta热核扩散算法的网络重建表明，与基底细胞相比，高度连接的网络具有更丰富的分化AEC。在从哮喘供体肺收集的基础AEC中进行的类似实验表明，与来自正常捐赠者的基础AEC相比，DE基因和与炎症相关的功能类别发生了实质性变化。在DAEC中，观察到了类似但更为轻微的差异。我们证明，心肌梗死后的AEC转录信号确定了对呼吸道粘膜炎症的启动和持续至关重要的基因和途径。基因表达在损伤后迅速发生，在分化的AEC中表达更深刻，在哮喘的AEC中基因表达发生改变。我们的数据表明，哮喘患者对损伤的早期反应有很大不同，尤其是在基本的呼吸道上皮细胞。
Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and differentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells. A select group of ~150 genes was in differential expression (DE) within 2–24 hr after MI, and enrichment analysis of these genes showed over-representation of functional categories related to inflammatory cytokines and chemokines. Network-based gene prioritization and network reconstruction using the PINTA heat kernel diffusion algorithm demonstrated highly connected networks that were richer in differentiated AEC compared to basal cells. Similar experiments done in basal AEC collected from asthmatic donor lungs demonstrated substantial changes in DE genes and functional categories related to inflammation compared to basal AEC from normal donors. In dAEC, similar but more modest differences were observed. We demonstrate that the AEC transcription signature after MI identifies genes and pathways that are important to the initiation and perpetuation of airway mucosal inflammation. Gene expression occurs quickly after injury and is more profound in differentiated AEC, and is altered in AEC from asthmatic airways. Our data suggest that the early response to injury is substantially different in asthmatic airways, particularly in basal airway epithelial cells.
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影响因子：
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DOI：
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发表时间：
2010-05-01
影响因子：
24.7
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