Postma Dirkje S, Timens Wim
Department of Pulmonology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9731 GZ Groningen, The Netherlands.
Proc Am Thorac Soc. 2006 Jul;3(5):434-9. doi: 10.1513/pats.200601-006AW.
Airway and lung tissue remodeling and fibrosis play an important role in the development of symptoms associated with lung function loss in asthma and chronic obstructive pulmonary disease (COPD). In the past decades, much attention has been paid to the inflammatory cellular process involved in airway remodeling in these two diseases. However, it is increasingly clear that resident cells contribute to airway and lung tissue remodeling and to associated fibrosis as well. This article deals with some new aspects and discusses the role of vasculature and vascular endothelial growth factor in the development of airway obstruction and airway wall fibrosis in asthma and COPD. Moreover, it addresses the extracellular matrix (ECM) turnover as present in both asthma and COPD. All components of lung ECM (collagen, elastic fibers, proteoglycans) have been shown to be potentially altered in these two diseases. Finally, the interaction between transforming growth factor (TGF), Smad signaling, and TGF in the ECM turnover will be discussed. We propose that ECM damage and repair contribute to airway and lung tissue pathology and that the vasculature may enhance this process. The localization of this process is dependent on the etiology of the disease (i.e., allergen-driven in asthma and smoke-driven in COPD) and the local environment in which the pathologic process takes place.
气道和肺组织重塑及纤维化在哮喘和慢性阻塞性肺疾病(COPD)中与肺功能丧失相关的症状发展过程中起着重要作用。在过去几十年里,人们对这两种疾病中参与气道重塑的炎症细胞过程给予了极大关注。然而,越来越明显的是,固有细胞也在气道和肺组织重塑以及相关纤维化过程中发挥作用。本文探讨了一些新的方面,并讨论了血管系统和血管内皮生长因子在哮喘和COPD气道阻塞及气道壁纤维化发展中的作用。此外,还阐述了哮喘和COPD中存在的细胞外基质(ECM)周转情况。肺ECM的所有成分(胶原蛋白、弹性纤维、蛋白聚糖)在这两种疾病中均已显示可能发生改变。最后,将讨论转化生长因子(TGF)、Smad信号传导以及TGF在ECM周转中的相互作用。我们提出,ECM损伤和修复导致气道和肺组织病变,而血管系统可能会加剧这一过程。该过程的定位取决于疾病的病因(即哮喘中由过敏原驱动,COPD中由烟雾驱动)以及病理过程发生的局部环境。