The role of the epithelium in airway remodeling in asthma.
The role of the epithelium in airway remodeling in asthma.
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DOI：
10.1513/pats.200907-067dp
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发表时间：
2009-12-01
期刊：
影响因子：
--
通讯作者：
Davies, Donna E
中科院分区：
文献类型：
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作者：
Davies, Donna E
支气管上皮细胞是外部环境的屏障，在保护肺的内部环境中起着至关重要的作用。它在上皮-间充质营养单位内起作用，以控制局部微环境并帮助维持组织稳态。然而，在哮喘中，这些稳态机制的慢性扰动导致气道结构的改变，称为重塑。现在认识到上皮损伤在驱动气道重塑中起关键作用。我们假设上皮对环境应激和损伤的敏感性以及受损的修复反应导致产生作用于下层间充质的信号，以传播和放大粘膜下层的炎症和重塑反应。对上皮的许多类型的挑战，包括病原体，过敏原，环境污染物，香烟烟雾，甚至机械力，可以引起上皮产生介质，这可以转化为间充质的重塑反应。已经鉴定了几种重要的重塑介质，最值得注意的是转化生长因子-β，其从受损/修复上皮释放或响应于炎症介质，如IL-13。在上皮下纤维化和与哮喘易感基因（一种去整合素和金属蛋白酶（ADAM））相关的潜在发病机制的背景下，考虑了上皮和底层间充质之间的串扰以驱动重塑反应33。
The bronchial epithelium is the barrier to the external environment and plays a vital role in protection of the internal milieu of the lung. It functions within the epithelial-mesenchymal trophic unit to control the local microenvironment and help maintain tissue homeostasis. However, in asthma, chronic perturbation of these homeostatic mechanisms leads to alterations in the structure of the airways, termed remodeling. Damage to the epithelium is now recognized to play a key role in driving airway remodeling. We have postulated that epithelial susceptibility to environmental stress and injury together with impaired repair responses results in generation of signals that act on the underlying mesenchyme to propagate and amplify inflammatory and remodeling responses in the submucosa. Many types of challenges to the epithelium, including pathogens, allergens, environmental pollutants, cigarette smoke, and even mechanical forces, can elicit production of mediators by the epithelium, which can be translated into remodeling responses by the mesenchyme. Several important mediators of remodeling have been identified, most notably transforming growth factor-beta, which is released from damaged/repairing epithelium or in response to inflammatory mediators, such as IL-13. The cross talk between the epithelium and the underlying mesenchyme to drive remodeling responses is considered in the context of subepithelial fibrosis and potential pathogenetic mechanisms linked to the asthma susceptibility gene, a disintegrin and metalloprotease (ADAM)33.