Dunsmore Sarah E
Harvard Medical School, Boston, MA, USA.
Int J Chron Obstruct Pulmon Dis. 2008;3(1):113-22. doi: 10.2147/copd.s1119.
Fundamental physical properties, such as the intrinsic recoil of the lung, are governed by the extracellular matrix. The prototypical roles of the matrix proteins, collagen and elastin, in pulmonary fibrosis and emphysema have long been recognized, and much research effort has been devoted to understanding mechanisms of extracellular matrix synthesis and turnover in the lung. Yet, despite extensive knowledge of the biochemical properties of collagen and elastin, none of the present clinical strategies for treating COPD directly target the extracellular matrix. From a matrix perspective, therapeutic interventions that limit elastic fiber destruction and/or restore function to damaged alveolar units merit particular consideration as clinical strategies for treating the emphysema component of COPD. Effective treatment of the bronchiolar component of COPD requires a better understanding of the relationship between airway fibrosis and airflow obstruction. Translating basic knowledge of extracellular matrix biology into the clinical venue will be essential in the development of new approaches to COPD treatment.
诸如肺的内在弹性回缩力等基本物理特性由细胞外基质所决定。基质蛋白胶原蛋白和弹性蛋白在肺纤维化和肺气肿中的典型作用早已为人所知,并且已经投入了大量研究精力来理解肺中细胞外基质合成与更新的机制。然而,尽管对胶原蛋白和弹性蛋白的生化特性有广泛了解,但目前治疗慢性阻塞性肺疾病(COPD)的临床策略均未直接针对细胞外基质。从基质的角度来看,限制弹性纤维破坏和/或恢复受损肺泡单位功能的治疗干预措施,作为治疗COPD肺气肿成分的临床策略值得特别考虑。有效治疗COPD的细支气管成分需要更好地理解气道纤维化与气流阻塞之间的关系。将细胞外基质生物学的基础知识转化为临床应用对于开发COPD治疗新方法至关重要。