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- Title
Role of Macrophage Metalloelastase (MMP-12) in Remodeling Following Bleomycin Induced Pulmonary Fibrosis.
- Authors
McClintock, Shannon D.; Barron, Adam G.; Warner, Roscoe L.; Nerusu, Kamalaker C.; Bhagavathula, Narasimharao; Varani, Jim; Johnson, Kent J.
- Abstract
Extracellular matrix (ECM) remodeling, involves a continuous degradation and clearing of damaged tissue and newly synthesized matrix, vital to tissue repair. In bleomycin model of pulmonary fibrosis there is a progressive increase in matrix formation and deposition that leads to impaired lung function. Matrix metalloproteases (MMP) are believed to play a key role in clearing damaged connective tissue so that normal structure and function can be reestablished. MMP-12 has previously been described as an essential factor involved in the proteolytic degradation of ECM. A progressive increase in airway thickening in both MMP-12 deficient (MMP-12 -/-) and MMP-12 sufficient (MMP-12 +/+) mice peaked at day 21. By day 45 airway thickening had returned to pre-challenge levels in MMP-12 +/+ mice, but was still significantly higher in MMP-12 -/- animals. Hydroxyproline measurements mirror these histological observations. At day 3 immunoreactive laminin in the BAL of MMP-12 +/+ and MMP-12 -/- animals was significantly increased, but by day 45 laminin levels in MMP-12 -/- BAL were still elevated while MMP-12 +/+ was back to pre-challenge levels. Therefore, the higher level of laminin, hydroxyproline and airway thickening in MMP-12 -/- mice, relative to MMP-12 +/+ animals suggests the continued accumulation of components in the alveolar basement membrane in the absence of functional MMP-12.
- Subjects
EXTRACELLULAR matrix; PULMONARY fibrosis; METALLOPROTEINASES; CONNECTIVE tissues; LABORATORY mice
- Publication
FASEB Journal, 2007, Vol 21, Issue 5, pA408
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.5.a408-d