Late Breaking Abstract - Role of matrix metalloproteinase-2 and -9 in experimental lung fibrosis in mice

Abstract

Idiopathic pulmonary fibrosis (IPF) is a diffuse parenchymal lung disease characterized by exuberant deposition of extracellular matrix (ECM) proteins in the lung interstitium, which contributes to substantial morbidity and mortality in IPF patients. Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endopeptidases, many of which have been implicated in the regulation of ECM degradation in lung fibrosis. However, the roles of MMP-2 and -9 (also termed gelatinases A and B) have not been explored in lung fibrosis so far. Patients with IPF exhibited significantly increased levels of MMP-2 and MMP-9 in lung tissue homogenates, relative to disease controls. Similarly, MMP-2 and MMP-9 proteins were significantly increased in the model of AdTGF-β1-induced lung fibrosis in mice, suggesting a role for these metalloproteinases in lung fibrogenesis. However, neither MMP-2 or MMP-9 deletion nor combined MMP-2/9 deletion did affect developing lung fibrosis, as assessed by lung histopathology, determination of lung collagen contents and invasive lung function testing. Together, our data suggest that gelatinases MMP-2 and MMP-9 are largely dispensable for lung fibrogenesis in the murine model of AdTGF-β1-induced lung fibrosis.