Journal
EXPERIMENTAL CELL RESEARCH
Volume 316, Issue 17, Pages 2993-3005Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2010.08.003
Keywords
Branching morphogenesis; Basement membrane; Matrix metalloproteinases; Kidney
Categories
Funding
- AHA established investigator award
- Department of Veterans Affairs
- George O'Brien Center
- [DK065123]
- [DK075594]
- [DK65123]
- [DK083187]
Ask authors/readers for more resources
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. (C) 2010 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available