Repair of naphthalene-induced acute tracheal injury by basal cells depends on β-catenin
Repair of naphthalene-induced acute tracheal injury by basal cells depends on β-catenin
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DOI：
10.1016/j.jtcvs.2013.10.039
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发表时间：
2014-07-01
影响因子：
6
通讯作者：
Hung, Shih-Chieh
中科院分区：
文献类型：
--
作者：
Hsu, Han-Shui;Liu, Chen-Chi;Hung, Shih-Chieh
目的：Wnt/β-catenin在出生后气道稳态和基底细胞功能中的作用知之甚少。本研究旨在探讨Wnt信号通路在基底细胞自我更新中的作用以及β-连环蛋白在萘致气管损伤后气管修复中的作用。通过免疫组化研究评估萘介导的分泌细胞耗竭后气管上皮的损伤和修复。Wnt和β-连环蛋白信号在基底细胞增殖的参与进行了研究，在体外expandment.Results：野生型小鼠气管上皮的免疫组化分析显示，克拉拉细胞分泌蛋白（CCSP+）和叉头盒转录因子（Fox-J1+）细胞的数量减少萘诱导损伤后第2天至第5天，这个细胞群再生的第10天。冲洗标记后，溴脱氧尿苷阳性（BrdU+）细胞和Ki 67+细胞在气管上皮中观察到的第2至5天，但没有在第10和21天。共聚焦显微镜观察K5+和BrdU+细胞显示Wnt 3a促进K5+细胞的增殖。野生型同窝小鼠和K5-Cre介导的β-catenin基因敲除小鼠气管上皮细胞中K5+和CCSP+的免疫组织化学分析显示，在第3天，所有小鼠中CCSP+细胞的数量减少。在第10天，CCSP+细胞存在于野生型同窝小鼠，但在条件性基因敲除mice.Conclusions：基底细胞作为干细胞在气管上皮，再生和维持气管上皮细胞在小鼠模型中的气管损伤。β-连环蛋白是气管上皮细胞增殖和自我更新所必需的。
Objectives: Little is known about the role of Wnt/beta-catenin in postnatal airway homeostasis and basal cell function. This study aimed to investigate the role of Wnt signaling in the self-renewal of basal cells and the involvement of beta-catenin in tracheal repair after naphthalene-induced injury.Methods: Mice were treated with naphthalene and injected with 4-hydroxytamoxifen. Injury and repair of the tracheal epithelium after naphthalene-mediated secretory cell depletion was assessed by a immunohistochemical study. The involvement of Wnt and beta-catenin signaling in basal cell proliferation was investigated during in vitro expansion.Results: Immunohistochemical analysis of tracheal epithelium in wild-type mice showed a reduction in the number of Clara cell secretory protein (CCSP+) and forkhead box transcription factor (Fox-J1+) cells on days 2 to 5 after naphthalene-induced injury; this cell population was regenerated by day 10. After flush labeling, bromodeoxyuridine-positive (BrdU+) cells and Ki67+ cells were observed in tracheal epithelium on days 2 to 5 but not on days 10 and 21. Confocal microscopy visualizing K5+ and BrdU+ cells showed that Wnt3a promotes proliferation of K5+ cells. Immunohistochemical analysis of K5+ and CCSP+ in tracheal epithelial cells from wild-type littermate and K5-Cre-mediated beta-catenin knock-out mice showed that on day 3, the number of CCSP+ cells was decreased in all mice. On day 10, CCSP+ cells were present in wild-type littermate mice but absent in conditional knock-out mice.Conclusions: Basal cells serve as stem cells in the tracheal epithelium, regenerating and maintaining tracheal epithelial cells in a mouse model of tracheal injury. beta-Catenin is required for proliferation and self-renewal of tracheal epithelial cells.