The importance of MT1-MMP during renal development

Abstract

The major goal of this thesis is to investigate the role of MT1-MMP in kidney development. Our results demonstrate that loss of MT1-MMP leads to a renal phenotype characterized by a moderate decrease in ureteric bud branching morphogenesis and a severe proliferation defect. This phenotype is independent of the MT1-MMP target, MMP-2. The kidneys of MT1-MMP-null mice have increased deposition of the major components of renal basement membranes: collagen IV, laminins, perlecan, and nidogen. Utilizing in vitro systems we demonstrate that MTI-MMP proteolytic activity is required for renal tubule cells to proliferate in three dimensional matrices and to migrate on the principal kidney basement membranes components. Together, these data suggest an important role for MT1-MMP in kidney development, which is mediated by its ability to regulate cell proliferation and migration by proteolytically cleaving kidney basement membrane extracellular matrix components. These finding have significantly improved the current knowledge of the role of MMPs renal development.