Figure 3. Hypothesis for the regulation of MMPs by asbestos. Asbestos exposure results in EGFR activation in epithelial cells and/or other growth factor receptors in fibroblasts, which leads to activation of PI3K/PKC/ERK1/2 and MMPs. MMPs once activated can further activate EGFR and downstream signaling pathways in epithelial cells. Inhibition of MMPs by GM6001 inhibited asbestos-induced ERK1/2 phosphorylation and EGFR activation in epithelial cells. EGF; EGFR, EGF receptor; ERK1/2, extracellular signal regulated kinase; GM6001, broad-spectrum MMP inhibitor; PI3K, phosphatidylinositol 3-kinase; PKC, protein kinase C delta.