HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/C659    most recent 00211.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Boyd, P. J. Articles by Haas, T. L. Search for Related Content PubMed PubMed Citation Articles by Boyd, P. J. Articles by Haas, T. L.

VASCULAR BIOLOGY

MAPK signaling regulates endothelial cell assembly into networks and expression of MT1-MMP and MMP-2

School of Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada

Submitted 28 April 2004 ; accepted in final form 26 October 2004

Microvascular endothelial cells embedded within three-dimensional (3D) type I collagen matrixes assemble into cellular networks, a process that requires the upregulation of membrane type 1 (MT1) matrix metalloproteinase (MMP) and MMP-2. The purpose of this study was to identify the signaling pathways responsible for the transcriptional activation of MT1-MMP and MMP-2 in endothelial cells in 3D collagen lattices. We hypothesized that the 3D type I collagen induction of MT1-MMP and MMP-2 is mediated by the mitogen-activated protein kinase family of enzymes. Here, we show that 3D type I collagen elicits a persistent increase in ERK1/2 and JNK activation and a decrease in p38 activation. Inhibition of ERK1/2 or JNK disrupted endothelial network formation in 3D type I collagen lattices, whereas inhibition of p38 promoted network formation. mRNA levels of both MT1-MMP and MMP-2 were attenuated by ERK1/2 inhibition but unaffected by either JNK or p38 inhibition. By contrast, expression of constitutively active MEK was sufficient to stimulate MMP-2 production in a monolayer of endothelial cells cultured on type I collagen. These results provide evidence that signaling through both ERK1/2 and JNK regulates endothelial assembly into cellular networks but that the ERK1/2 signaling cascade specifically regulates network formation and the production of both MT1-MMP and MMP-2 genes in response to 3D type I collagen.

membrane type 1; matrix metalloproteinases; angiogenesis; transcriptional control; extracellular matrix; mitogen-activated protein kinase

This article has been cited by other articles:

				H. S. Deshmukh, A. McLachlan, J. J. Atkinson, W. D. Hardie, T. R. Korfhagen, M. Dietsch, Y. Liu, P. Y. P. Di, S. C. Wesselkamper, M. T. Borchers, et al. Matrix Metalloproteinase-14 Mediates a Phenotypic Shift in the Airways to Increase Mucin Production Am. J. Respir. Crit. Care Med., November 1, 2009; 180(9): 834 - 845. [Abstract] [Full Text] [PDF]

				D. S. Markovic, K. Vinnakota, S. Chirasani, M. Synowitz, H. Raguet, K. Stock, M. Sliwa, S. Lehmann, R. Kalin, N. van Rooijen, et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion PNAS, July 28, 2009; 106(30): 12530 - 12535. [Abstract] [Full Text] [PDF]

				E. Ispanovic, D. Serio, and T. L. Haas Cdc42 and RhoA have opposing roles in regulating membrane type 1-matrix metalloproteinase localization and matrix metalloproteinase-2 activation Am J Physiol Cell Physiol, September 1, 2008; 295(3): C600 - C610. [Abstract] [Full Text] [PDF]

				U. Hiden, E. Glitzner, M. Ivanisevic, J. Djelmis, C. Wadsack, U. Lang, and G. Desoye MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and Tumor Necrosis Factor-{alpha} Levels Diabetes, January 1, 2008; 57(1): 150 - 157. [Abstract] [Full Text] [PDF]

				M. A. Zayed, W. Yuan, T. M. Leisner, D. Chalothorn, A. W. McFadden, M. D. Schaller, M. E. Hartnett, J. E. Faber, and L. V. Parise CIB1 Regulates Endothelial Cells and Ischemia-Induced Pathological and Adaptive Angiogenesis Circ. Res., November 26, 2007; 101(11): 1185 - 1193. [Abstract] [Full Text] [PDF]

				M. Milkiewicz, J. L. Doyle, T. Fudalewski, E. Ispanovic, M. Aghasi, and T. L. Haas HIF-1{alpha} and HIF-2{alpha} play a central role in stretch-induced but not shear-stress-induced angiogenesis in rat skeletal muscle J. Physiol., September 1, 2007; 583(2): 753 - 766. [Abstract] [Full Text] [PDF]

				P. Rocic, C. Kolz, R. Reed, B. Potter, and W. M. Chilian Optimal reactive oxygen species concentration and p38 MAP kinase are required for coronary collateral growth Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2729 - H2736. [Abstract] [Full Text] [PDF]

				K. Sanka, R. Maddala, D. L. Epstein, and P. V. Rao Influence of Actin Cytoskeletal Integrity on Matrix Metalloproteinase-2 Activation in Cultured Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2105 - 2114. [Abstract] [Full Text] [PDF]

				K. A. Galoian, N. Garamszegi, S. P. Garamszegi, and S. P. Scully Molecular Mechanism of Tenascin-C Action on Matrix Metalloproteinase-1 Invasive Potential Experimental Biology and Medicine, April 1, 2007; 232(4): 515 - 522. [Abstract] [Full Text] [PDF]

				E. Ispanovic and T. L. Haas JNK and PI3K differentially regulate MMP-2 and MT1-MMP mRNA and protein in response to actin cytoskeleton reorganization in endothelial cells Am J Physiol Cell Physiol, October 1, 2006; 291(4): C579 - C588. [Abstract] [Full Text] [PDF]