Nerve growth factor enhances Clara cell proliferation after lung injury
Nerve growth factor enhances Clara cell proliferation after lung injury
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DOI：
10.1183/09031936.00165508
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发表时间：
2010-07-01
影响因子：
24.3
通讯作者：
Nockher, W. A.
中科院分区：
文献类型：
--
作者：
Sonar, S. S.;Schwinge, D.;Nockher, W. A.
肺上皮细胞通过分泌各种细胞因子和生长因子促进伤口闭合。神经生长因子（NGF）在气道炎症中有很好的描述;然而，迄今为止，它在肺修复中的可能作用还没有被研究。为了研究NGF的修复功能，使用培养的肺泡上皮细胞进行体外实验，并使用萘-体外和体内实验均显示，损伤后气道上皮细胞增殖与炎症反应有关。依赖于NGF及其受体原肌球蛋白受体激酶A的表达。此外，NGF还增强肺泡II型细胞的体外迁移。在体内，在克拉拉细胞（NGFtg）中过度表达NGF的转基因小鼠没有发现克拉拉细胞表型的任何增殖或改变。然而，克拉拉细胞特异性损伤后，增殖增加的NGFtg和受损的抑制NGF。此外，神经生长因子还促进了I型胶原和纤连蛋白在体外和体内的表达在修复过程中，其中显着较高的水平被测量在再上皮NGFtg小鼠。我们的研究表明，神经生长因子促进体外肺上皮细胞的增殖和更新克拉拉细胞肺损伤后在体内。
The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far.To investigate the repair function of NGF, experiments were performed in vitro using cultured alveolar epithelial cells and in vivo using a naphthalene-induced model of Clara epithelial cell injury.Both in vitro and in vivo experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented in vitro migration of alveolar type II cells. In vivo, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin in vitro and in vivo during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice.Our study demonstrates that NGF promotes the proliferation of lung epithelium in vitro and the renewal of Clara cells following lung injury in vivo.