Shifren Adrian, Mecham Robert P
Department of Cell Biology and Physiology, Campus Box 8228, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Proc Am Thorac Soc. 2006 Jul;3(5):428-33. doi: 10.1513/pats.200601-009AW.
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.
肺的力学特性在很大程度上由发育过程中形成的结缔组织网络所决定。对肺力学和结构完整性最为重要的大分子是胶原蛋白、弹性蛋白和蛋白聚糖。纤维状胶原蛋白基因家族的成员提供了肺各个腔室的结构框架，而弹性纤维则提供弹性回缩力。弹性蛋白也是一个重要的结构成分，主要在肺泡阶段影响肺的发育。先前的研究已确凿表明，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。使疾病进程恶化的是肺细胞无法修复受损的弹性纤维，这导致肺功能永久受损并引发持续性退行性疾病。由于弹性纤维的大小、分子复杂性以及需要众多辅助蛋白来促进纤维组装，它们是最难修复的基质结构之一。最近关于弹性蛋白组装的研究，结合从基因失活研究以及人类疾病与弹性蛋白突变的关联中获得的对弹性纤维蛋白功能作用的新认识，为弹性蛋白稳态的分子和细胞复杂性提供了新的见解。
