The stumbling block in lung repair of emphysema: elastic fiber assembly.
The stumbling block in lung repair of emphysema: elastic fiber assembly.
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DOI：
10.1513/pats.200601-009aw
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发表时间：
2006-07-01
期刊：
影响因子：
--
通讯作者：
Mecham, Robert P
中科院分区：
文献类型：
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作者：
Shifren, Adrian;Mecham, Robert P
肺的机械特性在很大程度上由发育过程中形成的结缔组织网络决定。对肺力学和结构完整性最重要的大分子是胶原蛋白、弹性蛋白和蛋白聚糖。纤维胶原基因家族的成员提供各种肺室的结构框架，弹性纤维提供弹性回缩。弹性蛋白也是影响肺发育的重要结构成分，主要在肺泡阶段。以往的研究已明确表明，弹性蛋白降解是慢性阻塞性肺疾病发病机制中的关键步骤。加重疾病过程的是肺细胞无法修复受损的弹性纤维，这导致永久性肺功能受损和持续的退行性疾病。弹性纤维是最难修复的基质结构之一，因为它们的大小，分子复杂性，以及需要许多辅助蛋白来促进纤维组装。最近的研究结合弹性蛋白组装的新见解，从基因失活研究和人类疾病的联系，弹性蛋白突变的弹性纤维蛋白质的功能作用提供了新的见解的弹性蛋白稳态的分子和细胞的复杂性。
The mechanical properties of the lung are largely determined by the connective tissue networks laid down during development. The macromolecules most important for lung mechanics and structural integrity are collagen, elastin, and proteoglycans. Members of the fibrillar collagen gene family provide the structural framework of the various lung compartments and elastic fibers provide elastic recoil. Elastin is also an important architectural component that influences lung development, predominantly during the alveolar stage. Previous studies have conclusively shown that elastin degradation is a key step in the pathogenesis of chronic obstructive pulmonary disease. Exacerbating the disease process is the inability of lung cells to repair damaged elastic fibers, which leads to permanently compromised lung function and ongoing degenerative disease. Elastic fibers are among the most difficult matrix structures to repair because of their size, molecular complexity, and the requirement for numerous helper proteins to facilitate fiber assembly. Recent studies of elastin assembly combined with new insight into the functional role of elastic fiber proteins obtained from gene inactivation studies and linkage of human disease to elastin mutations provide new insight into the molecular and cellular complexities of elastin homeostasis.