MT1-MMP-mediated basement membrane remodeling modulates renal development

  • Riggins K
  • Mernaugh G
  • Su Y
 et al. 
  • 18

    Readers

    Mendeley users who have this article in their library.
  • 13

    Citations

    Citations of this article.

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. © 2010 Elsevier Inc.

Author-supplied keywords

  • Basement membrane
  • Branching morphogenesis
  • Kidney
  • Matrix metalloproteinases

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Karen S. Riggins

  • Glenda Mernaugh

  • Yan Su

  • Vito Quaranta

  • Naohiko Koshikawa

  • Motoharu Seiki

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free