Repair of tracheal epithelium by basal cells after chlorine-induced injury.
Repair of tracheal epithelium by basal cells after chlorine-induced injury.
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DOI：
10.1186/1465-9921-13-107
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发表时间：
2012-11-22
影响因子：
5.8
通讯作者：
Hoyle GW
中科院分区：
文献类型：
--
作者：
Musah S;Chen J;Hoyle GW
氯是一种广泛使用的有毒化合物，被认为是一种化学威胁剂。吸入氯气会损伤呼吸道上皮细胞，导致肺部异常。损伤上皮的有效修复是恢复正常肺结构和功能所必需的。本研究的目的是表征急性氯损伤后气管上皮的修复。将C57 BL/6小鼠暴露于氯气中，在暴露后第2、4、7和10天处死并收集气管前注射5-乙炔基-2 ′-脱氧尿苷（EdU）标记增殖细胞。通过EdU标记与三种主要气管上皮细胞类型的标记物[基底细胞的角蛋白5（K5）和角蛋白14（K14），Clara细胞的Clara细胞分泌蛋白（CCSP）和纤毛细胞的乙酰化微管蛋白（AcTub）]的共定位来检查分化上皮的气道修复和恢复。形态学分析用于测量假复层上皮的增殖和恢复。与中、远端气管相比，近端气管上皮修复最快、最广泛。在未暴露小鼠中，细胞增殖极轻微，所有基底细胞均表达K5，大多数切片中不存在表达K14的基底细胞。氯暴露导致Clara和纤毛细胞从气管上皮脱落。氯暴露后2 ~ 4天，表达K5和K14的基底细胞发生细胞增殖，K14细胞的数量急剧增加。在细胞增殖高峰期，修复气管的纤毛细胞和Clara细胞很少。在稍后的时间（第7-10天）检测到纤毛和Clara细胞标志物的表达，但在这些分化标志物重新表达的区域中未检测到细胞增殖。在第7-10天观察到纤维化病变，主要在气管远端。这些数据与存活的基底细胞作为祖细胞在氯损伤后重新填充气管上皮的模型一致。在剩下的基底细胞很少的区域，修复效率低下，导致气道纤维化。这些研究建立了一个模型，用于了解再生过程中的呼吸上皮细胞用于测试治疗气道损伤。
Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10), but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. The data are consistent with a model where surviving basal cells function as progenitor cells to repopulate the tracheal epithelium after chlorine injury. In areas with few remaining basal cells, repair is inefficient, leading to airway fibrosis. These studies establish a model for understanding regenerative processes in the respiratory epithelium useful for testing therapies for airway injury.
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克拉拉细胞：支气管上皮的祖细胞。
DOI：
10.1016/j.biocel.2009.09.002
发表时间：
2010-01
影响因子：
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作者：
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通讯作者：
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