School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
Pulm Pharmacol Ther. 2012 Apr;25(2):144-53. doi: 10.1016/j.pupt.2012.02.001. Epub 2012 Feb 16.
Extracellular matrix is generally increased in asthma, causing thickening of the airways which may either increase or decrease airway responsiveness, depending on the mechanical requirements of the deposited matrix. However, in vitro studies have shown that the altered extracellular matrix produced by asthmatic airway smooth muscle cells is able to induce increased proliferation of non-asthmatic smooth muscle cells, which is a process believed to contribute to airway hyper-responsiveness in asthma. Elastin is an extracellular matrix protein that is altered in asthmatic airways, but there has been no systematic investigation of the functional effect of these changes. This review reveals divergent reports of the state of elastin in the airway wall in asthma. In some layers of the airway it has been described as increased, decreased and/or fragmented, or unchanged. There is also considerable evidence for an imbalance of matrix metalloproteinases, which degrade elastin, and their respective inhibitors the tissue inhibitors of metalloproteinases, which collectively help to explain observations of both increased elastin and elastin fragments. A loss of lung elastic recoil in asthma suggests a mechanical role for disordered elastin in the aetiology of the disease, but extensive studies of elastin in other tissues show that elastin fragments elicit cellular effects such as increased proliferation and inflammation. This review summarises the current understanding of the role of elastin in the asthmatic airway.
细胞外基质在哮喘中通常会增加，导致气道变厚，这可能会增加或降低气道反应性，具体取决于沉积基质的机械要求。然而，体外研究表明，哮喘气道平滑肌细胞产生的改变的细胞外基质能够诱导非哮喘平滑肌细胞的增殖增加，这一过程被认为是导致哮喘气道高反应性的原因之一。弹性蛋白是一种细胞外基质蛋白，在哮喘气道中发生改变，但目前还没有对这些改变的功能影响进行系统研究。这篇综述揭示了哮喘气道中弹性蛋白状态的不同报告。在气道的某些层中，已经描述为增加、减少和/或碎片化，或不变。也有大量证据表明基质金属蛋白酶的失衡，这些酶降解弹性蛋白，以及它们各自的抑制剂金属蛋白酶组织抑制剂，共同有助于解释弹性蛋白的增加和弹性蛋白片段的观察结果。哮喘中肺弹性回缩的丧失表明弹性蛋白紊乱在疾病发病机制中的机械作用，但对其他组织中弹性蛋白的广泛研究表明，弹性蛋白片段会引起细胞增殖和炎症等效应。本综述总结了目前对弹性蛋白在哮喘气道中的作用的理解。
