Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation
Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation
复制标题
DOI：
10.1136/thx.2008.104133
复制
发表时间：
2009-09-01
期刊：
影响因子：
10
通讯作者：
Fisher, A. J.
中科院分区：
文献类型：
--
作者：
Borthwick, L. A.;Parker, S. M.;Fisher, A. J.
背景资料：上皮细胞异常修复是移植肺闭塞性细支气管炎（OB）气道重塑的关键事件。肺移植受者气道上皮细胞发生上皮细胞向间充质细胞转化（EMT）的潜力在培养和体内肺同种异体移植组织中进行评估。方法：单独或联合应用转化生长因子β 1（TGF-β 1）和肿瘤坏死因子α（TNF α）刺激后，评估上皮细胞和间充质细胞标志物表达的变化，并与未治疗的对照组进行比较。观察细胞存款、分泌基质金属蛋白酶（MMPs）和侵袭胶原的能力。上皮和间充质标记物的免疫定位进行了比较，在气道组织从稳定的收件人和OB。结果：未经处理的细胞保持上皮形态和表型。TGF-β（1）减少上皮标记物的表达，增加波形蛋白和纤连蛋白的表达，促进I型胶原和纤连蛋白沉积，并增加MMP-9的产生。与TNFa的共治疗显著地加重了EMT的表型和一些功能特征。气道上皮活检从收件人OB表现出显着增加染色间充质标记物和显着减少E-cadherin染色相比，稳定recipiers.Conclusions：这些观察表明，人类气道上皮细胞进行EMT的能力，并建议这种现象可能是一个潜在的联系之间的炎症损伤和TGF-β（1）驱动的气道重塑在OB的发展。
Background: Aberrant epithelial repair is a key event in the airway remodelling which characterises obliterative bronchiolitis (OB) in the transplanted lung. The potential for airway epithelium from lung transplant recipients to undergo epithelial to mesenchymal cell transition (EMT) was assessed in culture and in vivo in lung allograft tissue.Methods: Change in epithelial and mesenchymal marker expression was assessed after stimulation with transforming growth factor beta(1) (TGF-beta(1)) alone or in combination with tumour necrosis factor a (TNF alpha) and compared with untreated controls. The ability of cells to deposit extracellular matrix, secrete matrix metalloproteinases (MMPs) and invade collagen was investigated. Immunolocalisation of epithelial and mesenchymal markers was compared in airway tissue from stable recipients and those with OB.Results: Untreated cells maintained epithelial morphology and phenotype. TGF-beta(1) reduced expression of epithelial markers, increased expression of vimentin and fibronectin, promoted collagen I and fibronectin deposition and increased MMP-9 production. Co-treatment with TNFa dramatically accentuated phenotypic and some functional features of EMT. Airway epithelial biopsies from recipients with OB demonstrated significantly increased staining for mesenchymal markers and significantly reduced E-cadherin staining compared with stable recipients.Conclusions: These observations demonstrate the ability of human airway epithelium to undergo EMT and suggest this phenomenon may be a potential link between inflammatory injury and TGF-beta(1)-driven airway remodelling in the development of OB.