Mechanical forces induce an asthma gene signature in healthy airway epithelial cells
Mechanical forces induce an asthma gene signature in healthy airway epithelial cells
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DOI：
10.1038/s41598-020-57755-8
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发表时间：
2020-01-22
影响因子：
4.6
通讯作者：
Weiss, Scott T.
中科院分区：
文献类型：
--
作者：
Kilic, Ayse;Ameli, Asher;Weiss, Scott T.
支气管痉挛压迫支气管上皮，这种压迫压力与哮喘的发病机制有关。然而，这种压缩应力改变与疾病相关的途径的分子机制尚不清楚。利用来自非哮喘供体和哮喘供体的原代人支气管上皮细胞的气液界面培养，我们施加压缩应力，然后使用网络方法绘制分子相互作用组的变化。在来自非哮喘供体的细胞中，压迫本身足以诱导炎症、晚期修复和纤维化途径。值得注意的是，压缩后非哮喘细胞的分子谱再现了压缩前哮喘细胞的分子谱。总之，这些结果表明，即使在没有任何炎症刺激的情况下，机械压迫本身就足以诱导哮喘样的分子特征。
Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufficient to induce inflammatory, late repair, and fibrotic pathways. Remarkably, this molecular profile of non-asthmatic cells after compression recapitulated the profile of asthmatic cells before compression. Together, these results show that even in the absence of any inflammatory stimulus, mechanical compression alone is sufficient to induce an asthma-like molecular signature.