|
|
|
|
A more recent version of this article appeared on November 1, 2006 Originally published as MBC in Press, 10.1091/mbc.E06-06-0486 on October 18, 2006 Originally published as MBC in Press, 10.1091/mbc.E06-06-0486 on September 13, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 2, 2006
Revised on July 31, 2006
Accepted on August 31, 2006
*Canadian Institutes of Health Research Group in Matrix Dynamics, Faculty of Dentistry, and the
Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3E2, Canada;
University of British Columbia Centre for Blood Research, Vancouver, British Columbia V67 1Z3, Canada
Monitoring Editor: Asma Nusrat
Degradation of collagen is important for the physiological remodelling of connective tissues during growth and development, as well as in wound healing, inflammatory diseases and cancer cell invasion. In remodelling adult tissues, degradation of collagen occurs primarily through a phagocytic pathway. However, while various steps in the phagocytic pathway have been characterized, the enzyme required to initially fragment collagen fibrils for subsequent phagocytosis has not been identified. We have used laser confocal microscopy, TEM and biochemical assays to show that human fibroblasts initiate degradation of collagen through the collagenase activity of the membrane-bound metalloproteinase, MT1-MMP. Degradation of natural and reconstituted collagen substrates correlated with the expression of MT1-MMP, which was localized at sites of collagen cleavage at the surface of the cells and also within the cells, while collagen degradation was totally abrogated when MT1-MMP expression was blocked by siRNA treatment. In contrast to MT1-MMP, the gelatinolytic activity of MMP-2 was not required for collagen phagocytosis. These studies demonstrate a pivotal role of catalytically active MT1-MMP in preparing collagen fibrils for phagocytic degradation.
This article has been cited by other articles:
![]() |
X.-Y. Li, I. Ota, I. Yana, F. Sabeh, and S. J. Weiss Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase Mol. Biol. Cell, August 1, 2008; 19(8): 3221 - 3233. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nabavi, Y. Urukova, M. Cardelli, J. E. Aubin, and R. E. Harrison Lysosome Dispersion in Osteoblasts Accommodates Enhanced Collagen Production during Differentiation J. Biol. Chem., July 11, 2008; 283(28): 19678 - 19690. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-A. Cho, P. Osenkowski, H. Zhao, S. Kim, M. Toth, K. Cole, A. Aboukameel, A. Saliganan, L. Schuger, R. D. Bonfil, et al. The Inactive 44-kDa Processed Form of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Enhances Proteolytic Activity via Regulation of Endocytosis of Active MT1-MMP J. Biol. Chem., June 20, 2008; 283(25): 17391 - 17405. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nacu, I. G. Luzina, K. Highsmith, V. Lockatell, K. Pochetuhen, Z. A. Cooper, M. P. Gillmeister, N. W. Todd, and S. P. Atamas Macrophages Produce TGF-{beta}-Induced ({beta}-ig-h3) following Ingestion of Apoptotic Cells and Regulate MMP14 Levels and Collagen Turnover in Fibroblasts J. Immunol., April 1, 2008; 180(7): 5036 - 5044. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. A. Wagenaar-Miller, L. H. Engelholm, J. Gavard, S. S. Yamada, J. S. Gutkind, N. Behrendt, T. H. Bugge, and K. Holmbeck Complementary Roles of Intracellular and Pericellular Collagen Degradation Pathways In Vivo Mol. Cell. Biol., September 15, 2007; 27(18): 6309 - 6322. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. H. Madsen, L. H. Engelholm, S. Ingvarsen, T. Hillig, R. A. Wagenaar-Miller, L. Kjoller, H. Gardsvoll, G. Hoyer-Hansen, K. Holmbeck, T. H. Bugge, et al. Extracellular Collagenases and the Endocytic Receptor, Urokinase Plasminogen Activator Receptor-associated Protein/Endo180, Cooperate in Fibroblast-mediated Collagen Degradation J. Biol. Chem., September 14, 2007; 282(37): 27037 - 27045. [Abstract] [Full Text] [PDF] |
||||