title: Matrilysin (MMP-7) catalytic activity regulates β-catenin localization and signaling activation in lung epithelial cells.
abstract: Matrix metalloproteinase-7 (matrilysin, MMP-7) expression is increased in epithelium by bacterial infection, inflammation, fibrosis, and in a myriad 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. β-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 β-catenin function, we assessed effects of matrilysin catalytic activity on β-catenin localization and signaling activity in A549 cells and in bleomycin-induced lung injury in mice. We determined that matrilysin activity releases β-catenin from the cell membrane after which it is degraded in the cytosol. However, in the presence of a β-catenin stabilizing Wnt signal, β-catenin accumulated in the cytosol and activated a β-catenin luciferase promoter. Furthermore, β-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 β-catenin function in injured lung epithelium and may link extracellular proteolytic activity to cell junction disassembly and intracellular signaling.
authors.affiliation: Department of Pediatrics and Center for Lung Biology, University of Washington , Seattle, Washington , USA.
authors.forename: Cliff R
authors.initials: CR
authors.lastname: Rims
authors.forename: John K
authors.initials: JK
authors.lastname: McGuire
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D001761:Bleomycin; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000201:enzymology*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020545:Respiratory Mucosa / Q000201:enzymology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D001761:Bleomycin; D020783:Matrix Metalloproteinase 7