Published online before print April 25, 2002, doi: 10.1161/01.RES.0000019241.12929.EB
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Molecular Medicine |
Outside-In Signals Delivered by Matrix Metalloproteinase-1 Regulate Platelet Function
From the Departments of Vascular Surgery (S.W.G., L.W.K.), Internal Medicine (T.M.M., S.M.P., G.A.Z., A.S.W.), and Pathology (T.M.M.) and the Program in Human Molecular Genetics (S.L., L.A., D.J.M., J.M.F., T.M.M., G.A.Z., A.S.W.), University of Utah, Salt Lake City.
Correspondence to Spencer W. Galt, MD, and Andrew S. Weyrich, PhD, Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, 15 North 2030 East, Room 4220, University of Utah, Salt Lake City, Utah 84112-5330. E-mail sgalt{at}hsc.utah.edu and andy.weyrich@hmbg.utah.edu
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade extracellular matrix proteins. These enzymes are implicated in a variety of physiological and pathological events characterized by extracellular matrix remodeling. Recent studies suggest that MMPs may have a signaling capacity, but direct evidence supporting this concept is lacking. In the present study, we demonstrate that outside-in signals delivered by exogenous MMP-1 (interstitial collagenase) markedly increase the number of tyrosine-phosphorylated proteins in platelets. Active MMP-1 also targets ß3 integrins to areas of cell contact and primes platelets for aggregation. Examination of the endogenous enzyme demonstrated that activated platelets process latent MMP-1 into its active form. Neutralization of MMP-1 activity with MMP inhibitors or specific blocking antibodies markedly attenuates agonist-induced phosphorylation of intracellular proteins, movement of ß3 integrins to cell contact points, and intercellular aggregation. The finding that MMP-1 is rapidly activated in platelets and controls functional responses identifies a new role for this metalloproteinase as a signaling molecule that regulates thrombotic events.
Key Words: matrix metalloproteinases • platelets • signaling • thrombosis
This article has been cited by other articles:
 |
|
 |
|
  Y.-C. Cheng, W.-H. L. Kao, B. D. Mitchell, J. R. O'Connell, H. Shen, P. F. McArdle, Q. Gibson, K. A. Ryan, A. R. Shuldiner, and T. I. Pollin Genome-Wide Association Scan Identifies Variants near Matrix Metalloproteinase (MMP) Genes on Chromosome 11q21-22 Strongly Associated With Serum MMP-1 Levels Circ Cardiovasc Genet, August 1, 2009; 2(4): 329 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Menchen, I Marin-Jimenez, E G Arias-Salgado, T Fontela, P Hernandez-Sampelayo, M C G. Rodriguez, and N V Butta Matrix metalloproteinase 9 is involved in Crohn's disease-associated platelet hyperactivation through the release of soluble CD40 ligand Gut, July 1, 2009; 58(7): 920 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Foulks, G. K. Marathe, N. Michetti, D. M. Stafforini, G. A. Zimmerman, T. M. McIntyre, and A. S. Weyrich PAF-acetylhydrolase expressed during megakaryocyte differentiation inactivates PAF-like lipids Blood, June 25, 2009; 113(26): 6699 - 6706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ho-Tin-Noe, T. Goerge, S. M. Cifuni, D. Duerschmied, and D. D. Wagner Platelet Granule Secretion Continuously Prevents Intratumor Hemorrhage Cancer Res., August 15, 2008; 68(16): 6851 - 6858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Italiano Jr, J. L. Richardson, S. Patel-Hett, E. Battinelli, A. Zaslavsky, S. Short, S. Ryeom, J. Folkman, and G. L. Klement Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet {alpha} granules and differentially released Blood, February 1, 2008; 111(3): 1227 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Andrews, D. Karunakaran, E. E. Gardiner, and M. C. Berndt Platelet Receptor Proteolysis: A Mechanism for Downregulating Platelet Reactivity Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1511 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Weyrich, M. M. Denis, H. Schwertz, N. D. Tolley, J. Foulks, E. Spencer, L. W. Kraiss, K. H. Albertine, T. M. McIntyre, and G. A. Zimmerman mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets Blood, March 1, 2007; 109(5): 1975 - 1983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Boylan, M. C. Berndt, M. L. Kahn, and P. J. Newman Activation-independent, antibody-mediated removal of GPVI from circulating human platelets: development of a novel NOD/SCID mouse model to evaluate the in vivo effectiveness of anti-human platelet agents Blood, August 1, 2006; 108(3): 908 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Alonso-Escolano, C. Medina, K. Cieslik, A. Radomski, P. Jurasz, M. J. Santos-Martinez, T. Jiffar, P. Ruvolo, and M. W. Radomski Protein Kinase C{delta} Mediates Platelet-Induced Breast Cancer Cell Invasion J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 373 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Medina, P. Jurasz, M. J. Santos-Martinez, S. S. Jeong, T. Mitsky, R. Chen, and M. W. Radomski Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 739 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kisucka, C. E. Butterfield, D. G. Duda, S. C. Eichenberger, S. Saffaripour, J. Ware, Z. M. Ruggeri, R. K. Jain, J. Folkman, and D. D. Wagner Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage PNAS, January 24, 2006; 103(4): 855 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Haulica, W. Bild, and D. N Serban Review: Angiotensin Peptides and their Pleiotropic Actions Journal of Renin-Angiotensin-Aldosterone System, September 1, 2005; 6(3): 121 - 131. [Abstract] [PDF]
|
|
|
|
 |
|
 G. A. Limb, K. Matter, G. Murphy, A. D. Cambrey, P. N. Bishop, G. E. Morris, and P. T. Khaw Matrix Metalloproteinase-1 Associates with Intracellular Organelles and Confers Resistance to Lamin A/C Degradation during Apoptosis Am. J. Pathol., May 1, 2005; 166(5): 1555 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]
|
|
|
|
|
|
G. Stephens, Y. Yan, M. Jandrot-Perrus, J.-L. Villeval, K. J. Clemetson, and D. R. Phillips Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen Blood, January 1, 2005; 105(1): 186 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Gardiner, J. F. Arthur, M. L. Kahn, M. C. Berndt, and R. K. Andrews Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase Blood, December 1, 2004; 104(12): 3611 - 3617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Ryan and C. D. Sigmund ACE, ACE Inhibitors, and Other JNK Circ. Res., January 9, 2004; 94(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
K. Kohlstedt, R. P. Brandes, W. Muller-Esterl, R. Busse, and I. Fleming Angiotensin-Converting Enzyme Is Involved in Outside-In Signaling in Endothelial Cells Circ. Res., January 9, 2004; 94(1): 60 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Bergmeier, P. C. Burger, C. L. Piffath, K. M. Hoffmeister, J. H. Hartwig, B. Nieswandt, and D. D. Wagner Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets Blood, December 1, 2003; 102(12): 4229 - 4235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jurasz, D. Alonso, S. Castro-Blanco, F. Murad, and M. W. Radomski Generation and role of angiostatin in human platelets Blood, November 1, 2003; 102(9): 3217 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B Jones, D. C Sane, and D. M Herrington Matrix metalloproteinases: A review of their structure and role in acute coronary syndrome Cardiovasc Res, October 1, 2003; 59(4): 812 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wang, T. M. Leisner, and L. V. Parise Platelet {alpha}2{beta}1 integrin activation: contribution of ligand internalization and the {alpha}2-cytoplasmic domain Blood, August 15, 2003; 102(4): 1307 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Heo, S. H. Kim, K. Y. Lee, E. H. Kim, C. K. Chu, and J. M. Nam Increase in Plasma Matrix Metalloproteinase-9 in Acute Stroke Patients With Thrombolysis Failure Stroke, June 1, 2003; 34 (6): e48 - e50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jurasz, A. W.Y. Chung, A. Radomski, and M. W. Radomski Nonremodeling Properties of Matrix Metalloproteinases: The Platelet Connection Circ. Res., May 31, 2002; 90(10): 1041 - 1043. [Full Text] [PDF]
|
|