TY - JOUR
T1 - The stumbling block in lung repair of emphysema
T2 - Elastic fiber assembly
AU - Shifren, Adrian
AU - Mecham, Robert P.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Elastin
KW - Elastin mutations
KW - Emphysema
KW - Extracellular matrix
KW - Repair
UR - http://www.scopus.com/inward/record.url?scp=33745845118&partnerID=8YFLogxK
U2 - 10.1513/pats.200601-009AW
DO - 10.1513/pats.200601-009AW
M3 - Article
C2 - 16799087
AN - SCOPUS:33745845118
SN - 1546-3222
VL - 3
SP - 428
EP - 433
JO - Proceedings of the American Thoracic Society
JF - Proceedings of the American Thoracic Society
IS - 5
ER -