These findings establish that the two commonly proposed orthologs of MMP1, Mmp1a and Mmp1b, provide substantial limitations for use in examining MMP1 induced lung disease in mouse models of cigarette smoke emphysema.
SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD.
Previously, we reported that smoke exposure leads to the induction of matrix metalloproteinase-1 (MMP-1) through the activation of ERK1/2, which is critical to the development of emphysema.
GSTP1, EPHX1, and MMP1 polymorphisms were associated with the densitometric, apical-predominant distribution of emphysema (p value range = 0.001-0.050).
The hybrid mice demonstrated an identical emphysematous phenotype as the MMP-1 transgenic mice, indicating that the degradation of type I collagen was not essential to the development of emphysema in these mice.
This study provides evidence that MMP-1 induces progressive adult-onset emphysema by the selective degradation of type III collagen within the alveolar wall.
Immunohistochemistry studies localized MMP-1 to the Type II pneumocyte in patients with emphysema and not normal control subjects or smokers without emphysema.
Macrophages from bronchoalveolar lavage fluid of 10 patients with emphysema and 10 normal volunteers were maintained in vitro for 24 h and assessed semiquantitatively for mRNA transcript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase.
This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process.