title: MT1-MMP-mediated basement membrane remodeling modulates renal development.
abstract: Extracellular matrix (ECM) remodeling regulates multiple cellular functions required for normal development and tissue repair. Matrix metalloproteinases (MMPs) are key mediators of this process and membrane targeted MMPs (MT-MMPs) in particular have been shown to be important in normal development of specific organs. In this study we investigated the role of MT1-MMP in kidney development. We 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. The kidneys of MT1-MMP-null mice have increased deposition of collagen IV, laminins, perlecan, and nidogen and the phenotype is independent of the MT-1MMP target, MMP-2. Utilizing in vitro systems we demonstrated that MTI-MMP proteolytic activity is required for renal tubule cells to proliferate in three dimensional matrices and to migrate on collagen IV and laminins. 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 components.
authors: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Karen S
authors: KS
authors: Riggins
authors: Glenda
authors: G
authors: Mernaugh
authors: Yan
authors: Y
authors: Su
authors: Vito
authors: V
authors: Quaranta
authors: Naohiko
authors: N
authors: Koshikawa
authors: Motoharu
authors: M
authors: Seiki
authors: Ambra
authors: A
authors: Pozzi
authors: Roy
authors: R
authors: Zent
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D005109:Extracellular Matrix; D007668:Kidney / Q000166:cytology / Q000254:growth & development*; D053511:Matrix Metalloproteinase 14 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: C507096:Mmp14 protein, mouse; D053511:Matrix Metalloproteinase 14