Role of human airway smooth muscle in altered extracellular matrix production in asthma
Role of human airway smooth muscle in altered extracellular matrix production in asthma
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DOI：
10.1046/j.1440-1681.2001.03426.x
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发表时间：
2001-03-01
影响因子：
2.9
通讯作者：
Johnson, PRA
中科院分区：
文献类型：
--
作者：
Johnson, PRA
1.哮喘中潜在的异常尚不完全清楚;然而，炎症、气道重塑和支气管高反应性是关键因素。微血管渗漏的血浆渗出物在气道重塑中起重要作用，包括细胞外基质（ECM）蛋白沉积/分解和气道平滑肌（ASM）增生/肥大. ECM是一个复杂的大分子网络，形成了气道的“支架”。这种支架不仅作为机械支持，在维持气道功能和结构中起着至关重要的作用，而且它也是一个动态和复杂的网络，有可能影响细胞功能，包括迁移，分化和增殖的一些细胞类型。3.在哮喘气道中，ECM蛋白质的谱改变。胶原I、III、V、纤连蛋白、腱生蛋白、透明质酸、多能蛋白聚糖和层粘连蛋白α 2/β 2的沉积增加，而胶原IV和弹性蛋白的沉积减少。哮喘气道内ECM谱的这种不平衡可能是由于：（i）ECM蛋白的从头合成增加;（ii）其降解酶即基质金属蛋白酶（MMP）的活性降低;或（iii）金属蛋白酶的组织特异性抑制剂（TIMP）的上调。哮喘的特征之一是气道内ASM的量增加。平滑肌内和周围的ECM蛋白/MMP/TIMP可能在这种增加的生长中起贡献作用。目前哮喘治疗在预防或逆转气道ECM变化中的作用是最近才引起关注的一个领域，大部分体内工作集中在皮质类固醇的作用上。在这篇综述中提出的证据表明，ASM可能会影响自己的环境/增殖，通过生产ECM蛋白，MMP和TIMP。需要进一步的研究来充分了解ASM在ECM蛋白、MMP和TIMP的产生中的作用以及它们在哮喘潜在机制中的潜在影响。
1. The underlying abnormality in asthma is not fully understood; however, inflammation, airway remodelling and bronchial hyperresponsiveness are key factors. The plasma exudate from the microvascular leakage plays a significant role in remodelling, which includes extracellular matrix (ECM) protein deposition/breakdown and airway smooth muscle (ASM) hyperplasia/ hypertrophy.2. The ECM is an intricate network of macromolecules that forms the 'scaffolding' of the airways. This scaffolding not only acts as mechanical support that plays a crucial role in the maintenance of airway function and structure, but it is also a dynamic and complex network that has the potential to influence cellular function, including migration, differentiation and proliferation of a number of cell types.3. In asthmatic airways, the profile of ECM proteins is altered. The deposition of collagen I, III, V, fibronectin, tenascin, hyaluronan, versican and laminin alpha2/beta2 is increased, whereas the deposition of collagen IV and elastin is decreased.4. This imbalance in the ECM profile within the asthmatic airway could be due to: (i) increased de novo synthesis of ECM proteins; (ii) decreased activity of its degrading enzymes, namely matrix metalloproteinases (MMP); or (iii) upregulation of the tissue-specific inhibitors of metalloproteinases (TIMP).5. One of the characteristic features of asthma is an increase in the amount of ASM within the airways. The ECM proteins/MMP/TIMP in and around the smooth muscle may play a contributory role in this increased growth.6. The role of current asthma treatments in the prevention or reversal of airway ECM changes is an area that has only recently become of interest, with the majority of the in vivo work focusing on the effects of corticosteroids.7. The evidence presented in this review indicates that the ASM may influence its own environment/proliferation through the production of ECM proteins, MMP and TIMP. Further studies are needed to fully understand the role of the ASM in the production of ECM proteins, MMP and TIMP and their potential influence in the mechanisms underlying asthma.