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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-08242010-223415 |
| Date | 01 September 2010 |
| Creators | Riggins, Karen Shakita |
| Contributors | Vito Quaranta, Raymond Harris, Billy Hudson, Ambra Pozzi, Roy Zent |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-08242010-223415/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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