Collagenolysis-dependent Angiogenesis Mediated by Matrix Metalloproteinase-13 (Collagenase-3)

• DOI: 10.1074/jbc.m313617200
• Publication Date: 2004-06-18T19:10:51Z
• Authors: Andries Zijlstra; Ronald T. Aimes; Dan Zhu; Karine Regazzoni; Tatyana Kupriyanova; Marco Seandel; Elena I. Deryugina; James P. Quigley
• Keywords: Matrix metalloproteinase inhibitor; Matrix (chemical analysis)

We have demonstrated previously that new blood vessel formation induced by angiogenic growth factors in onplants placed on the chorioallantoic membrane (CAM) of chick embryos is critically dependent cleavage fibrillar collagen a unidentified interstitial collagenase. In present study we used quantitative CAM angiogenesis system to search for and functionally characterize host avian collagenases responsible remodeling associated with angiogenesis. Among matrix metalloproteinases (MMPs) identified onplant tissue, chicken MMP-13 (chMMP-13) was only enzyme whose induction expression coincided onset formation. The chMMP-13 cDNA has been cloned recombinantly expressed. protein purified, characterized vitro, examined situ CAM. MMP-13-positive cells appear shortly after stimulation then accumulate tissue. Morphologically, chMMP-13-containing as hematopoietic monocyte/macrophage lineage. proenzyme rapidly efficiently activated through urokinase plasminogen activator/plasminogen/plasmin cascade into collagenase capable cleaving native but not (r/r) mutant collagenase-resistant collagen. Surprisingly, nanogram levels purified elicit an response comparable factors. chMMP-13-mediated blocked select protease inhibitors indicating plasmin-activated can function factor vivo. Altogether, results this extend physiological role MMP-13, cartilage/bone resorption, involved cascade.