Matrilysin (MMP-7) catalytic activity regulates β-catenin localization and signaling activation in lung epithelial cells.

Matrix metalloproteinase-7 (matrilysin, MMP-7) expression is increased in epithelium by bacterial infection, inflammation, fibrosis, and in amyriad of carcinomas. It functions to degrade extracellular matrix and other pericellular substrates including the adherens junction protein E-cadherin to promote wound healing and tissue remodeling. beta-catenin functions as both a structural component of adherens junctions and as an intracellular signaling molecule. To assess if matrilysin-mediated disassembly of adherens junctions regulates beta-catenin function, we assessed effects of matrilysin catalytic activity on beta-catenin localization and signaling activity in A549 cells and in bleomycin-induced lung injury in mice. We determined that matrilysin activity releases beta-catenin from the cell membrane after which it is degraded in the cytosol. However, in the presence of a beta-catenin stabilizing Wnt signal, beta-catenin accumulated in the cytosol and activated a beta-catenin luciferase promoter. Furthermore, beta-catenin nuclear translocation and activation was impaired in matrilysin-null mice when compared to wild-type mice after bleomycin-induced lung injury. These results show identify matrilysin as a regulator of beta-catenin function in injured lung epithelium and may link extracellular proteolytic activity to cell junction disassembly and intracellular signaling.