Epithelial plasticity in COPD results in cellular unjamming due to an increase in polymerized actin.
Epithelial plasticity in COPD results in cellular unjamming due to an increase in polymerized actin.
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DOI：
10.1242/jcs.258513
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发表时间：
2022-02-15
影响因子：
4
通讯作者：
Sidhaye VK
中科院分区：
文献类型：
--
作者：
Ghosh B;Nishida K;Chandrala L;Mahmud S;Thapa S;Swaby C;Chen S;Khosla AA;Katz J;Sidhaye VK
气道上皮细胞受到诸如香烟烟雾（CS）的损伤，这是慢性阻塞性肺疾病（COPD）的主要原因，并且作为研究细胞可塑性的极好模型。在这里，我们发现CS暴露和COPD患者衍生的上皮细胞（CHBE）显示细胞可塑性的定量证据，失去了专门的顶端功能和转录谱提示部分上皮间充质转化（PEMT），尽管有不同的细胞运动指示细胞解扰。由于肌动蛋白切割蛋白cofilin-1的丢失，这些受损/患病的细胞具有增加的聚合肌动蛋白部分。我们观察到，减少聚合肌动蛋白恢复堵塞状态在CHBE和CS暴露的上皮细胞，表明聚合肌动蛋白的分数是至关重要的解除堵塞上皮细胞。我们的动能谱分析表明，cofilin-1的损失导致unjamming，类似于CS暴露和CHBE细胞中所看到的。研究结果表明，在对慢性损伤的反应中，尽管上皮细胞显示出pEMT的证据，但它们的运动与细胞的解除干扰更一致。肌动蛋白聚合的抑制剂纠正了单层膜的不受干扰的特性。总结：COPD患者来源的上皮细胞显示出可量化的可塑性，其通过重复的体外烟雾暴露复制，并且是由肌动蛋白聚合物质量增加和cofilin-1损失引起的。
The airway epithelium is subjected to insults such as cigarette smoke (CS), a primary cause of chronic obstructive pulmonary disease (COPD) and serves as an excellent model to study cell plasticity. Here, we show that both CS-exposed and COPD-patient derived epithelia (CHBE) display quantitative evidence of cellular plasticity, with loss of specialized apical features and a transcriptional profile suggestive of partial epithelial-to-mesenchymal transition (pEMT), albeit with distinct cell motion indicative of cellular unjamming. These injured/diseased cells have an increased fraction of polymerized actin, due to loss of the actin-severing protein cofilin-1. We observed that decreasing polymerized actin restores the jammed state in both CHBE and CS-exposed epithelia, indicating that the fraction of polymerized actin is critical in unjamming the epithelia. Our kinetic energy spectral analysis suggests that loss of cofilin-1 results in unjamming, similar to that seen with both CS exposure and in CHBE cells. The findings suggest that in response to chronic injury, although epithelial cells display evidence of pEMT, their movement is more consistent with cellular unjamming. Inhibitors of actin polymerization rectify the unjamming features of the monolayer. Summary: COPD-patient-derived epithelia show quantifiable plasticity that is replicated by repetitive in vitro smoke exposure and is caused by increased actin polymer mass and loss of cofilin-1.
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影响因子：
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影响因子：
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10.1152/ajplung.00050.2020
发表时间：
2020-05-01
影响因子：
4.9
作者：
Ghosh, Baishakhi;Park, Bongsoo;Sidhaye, Venkataramana K.
通讯作者：
Sidhaye, Venkataramana K.
影响因子：
2.2
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