The stumbling block in lung repair of emphysema: elastic fiber assembly.
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.
Shifren
Adrian
A
Department of Cell Biology and Physiology, Campus Box 8228, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Mecham
Robert P
RP
D000818:Animals; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D004547:Elastic Tissue / Q000378:metabolism / Q000503:physiopathology*; D004548:Elasticity; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011656:Pulmonary Emphysema / Q000378:metabolism* / Q000503:physiopathology
D004247:DNA; D004549:Elastin