Effects of growth factors and extracellular matrix on survival of human airway smooth muscle cells
Effects of growth factors and extracellular matrix on survival of human airway smooth muscle cells
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DOI：
10.1165/ajrcmb.25.5.4605
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发表时间：
2001-11-01
影响因子：
6.4
通讯作者：
Hall, IP
中科院分区：
文献类型：
--
作者：
Freyer, AM;Johnson, SR;Hall, IP
气道重塑使长期哮喘复杂化。其特征是气道平滑肌细胞（SMC）数量增加以及气道细胞外基质（ECM）类型增加和改变。尽管气道中 SMC 的数量取决于细胞增殖和细胞死亡的平衡，但迄今为止的研究主要集中在影响 SMC 增殖的因素上。在这里，我们报告了第一项关于气道 SMC 存活因子的研究：这些细胞接收到强烈的存活信号，该信号不依赖于已知的生长因子丝裂原。我们确定了 ECM 因子纤连蛋白、层粘连蛋白以及 I 型和 IV 型胶原蛋白作为重要的抗凋亡元件，并表征了培养的 SMC 上 ECM 受体（整合素）的表达。功能性阻断抗体和肽研究表明，α (5)β (1) 整合素是这些细胞中 ECM 衍生生存信号的重要转导因子。共聚焦显微镜证实了离散 ECM 因子对 SMC 表型（尤其是细胞骨架）的显着影响。总之，我们的数据通过概述气道 SMC 的关键生存因素并强调细胞-基质相互作用对细胞死亡和表型的影响，提高了对气道重塑机制的理解。
Airway remodeling complicates longstanding asthma. It is characterized by an increase in the number of airway smooth muscle cells (SMCs) as well as an increase in and alteration of the type of extra-cellular matrix (ECM) in the airways. Although the number of SMCs in the airways depends on the balance of cell proliferation and cell death, studies to date have concentrated on factors affecting SMC proliferation. Here we report the first study on airway SMC survival factors: these cells receive a strong survival signal, which is not dependent on the known growth factor mitogens. We identified the ECM factors fibronectin, laminin, and collagens I and IV as important anti-apoptotic elements, and characterized the expression of the ECM receptors (integrins) on cultured SMC. Functionally blocking antibody and peptide studies revealed the alpha (5)beta (1) integrin to be an important transducer of the ECM-derived survival signal in these cells. Confocal microscopy confirmed the striking effects that discrete ECM factors have on SMC phenotype, notably the cytoskeleton. In summary, our data improves the understanding of the mechanisms underlying airway remodeling by outlining the key survival factors for airway SMC and by highlighting the impact of the cell-matrix interactions on cell death and phenotype.