| Literature DB >> 20727881 |
Karen S Riggins1, Glenda Mernaugh, Yan Su, Vito Quaranta, Naohiko Koshikawa, Motoharu Seiki, Ambra Pozzi, Roy Zent.
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.Entities:
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Year: 2010 PMID： 20727881 PMCID： PMC2945451 DOI： 10.1016/j.yexcr.2010.08.003
Source DB: PubMed Journal: Exp Cell Res ISSN： 0014-4827 Impact factor: 3.905