Role for cathepsin K in emphysema in smoke-exposed guinea pigs.
The protease-antiprotease imbalance in the lung plays an important role in the pathogenesis of smoke-induced emphysema. The aim of this study was to characterize the proteolytic responses leading to emphysema formation in the guinea pig smoke exposure model. Guinea pigs were exposed to cigarette smoke for 1, 2, 4, 8, and 12 weeks. Age-matched guinea pigs exposed to room air served as controls. Cigarette smoke induced inflammation after 4 weeks and generated emphysematous changes in the guinea pigs after 12 weeks of smoke exposure. Increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases was demonstrated post cigarette smoke exposure. A decrease in elastin and collagen and the loss of type III collagen were observed in the alveolar wall of smoke-exposed guinea pigs. Interestingly, no change was seen in the expression of collagenolytic matrix metalloproteinases. Furthermore, the authors observed a 3-fold increase in cathepsin K activity in the lungs of smoke-exposed guinea pigs. The significance of this finding was supported by human studies that demonstrate increased expression of cathepsin K in the lungs of patients with emphysema. Elevation of cathepsin K in guinea pig lungs after smoke exposure likely constitutes a critical event leading to the disruption of lung extracellular matrix in this model.
Golovatch
Polina
P
Division of Molecular Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Mercer
Becky A
BA
Lemaître
Vincent
V
Wallace
Alison
A
Foronjy
Robert F
RF
D'Armiento
Jeanine
J
D000818:Animals; D056657:Cathepsin K / Q000032:analysis* / Q000502:physiology; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D007249:Inflammation / Q000209:etiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors
D012906:Smoke; D003094:Collagen; D004549:Elastin; D020928:Mitogen-Activated Protein Kinases; D056657:Cathepsin K