Fig. 1

Putative roles of some MMPs in pulmonary fibrosis. In activated alveolar epithelial cells, MMP-7 cleaves osteopontin and potentiates its function which in turn upregulates and activates MMP-7. In this profibrotic cross-talk, osteopontin upregulates the expression of ECM proteins. MMP-19 co-localizes and co-regulates with COX2 which end product, prostaglandin E2, is a potent suppressor of fibroblast proliferation and collagen production. Deficiency of MMP-19 in fibroblasts results in the upregulation of several profibrotic genes and pathways that provoke an increase of fibroblast migration and proliferation and a decrease of these processes in epithelial cells. Upregulation of MMP-1 in alveolar epithelial cells represses mitochondrial respiration and oxidative stress, while promotes cell proliferation, migration, and HIF-1α expression, and induces an anti-apoptotic phenotype. MMP3 induces EMT, and MMP9 is upregulated by TGF β in Thy-1 negative fibroblasts which in turn activates this growth factor. OPN = osteopontin; COX2 = cyclooxygenase 2; ECM = extracellular matrix; EMT = epithelial to mesenchymal transition