scholarly journals Type I Collagen-induced MMP-2 Activation Coincides with Up-regulation of Membrane Type 1-Matrix Metalloproteinase and TIMP-2 in Cardiac Fibroblasts

2003 ◽  
Vol 278 (47) ◽  
pp. 46699-46708 ◽  
Author(s):  
Chun Guo ◽  
Lucia Piacentini
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Cardiac Fibroblasts ◽  
Type I ◽  
Membrane Type

scholarly journals Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Ubiquitination at Lys581Increases Cellular Invasion through Type I Collagen

2012 ◽  
Vol 287 (14) ◽  
pp. 11533-11545 ◽  
Author(s):  
Patricia A. Eisenach ◽  
Pedro Corrêa de Sampaio ◽  
Gillian Murphy ◽  
Christian Roghi
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Type I ◽  
Cellular Invasion ◽  
Membrane Type

scholarly journals Type I Collagen Abrogates the Clathrin-mediated Internalization of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) via the MT1-MMP Hemopexin Domain

2005 ◽  
Vol 281 (10) ◽  
pp. 6826-6840 ◽  
Author(s):  
Marc A. Lafleur ◽  
Francesca A. Mercuri ◽  
Neeracha Ruangpanit ◽  
Motoharu Seiki ◽  
Hiroshi Sato ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Type I ◽  
Membrane Type ◽  
Hemopexin Domain

scholarly journals Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

2008 ◽  
Vol 19 (8) ◽  
pp. 3221-3233 ◽  
Author(s):  
Xiao-Yan Li ◽  
Ichiro Ota ◽  
Ikuo Yana ◽  
Farideh Sabeh ◽  
Stephen J. Weiss
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Cell Function ◽  
Catalytic Domain ◽  
Transmembrane Domain ◽  
Type I ◽  
Cell Trafficking ◽  
Membrane Type

Membrane type-1 matrix metalloproteinase (MT1-MMP) drives cell invasion through three-dimensional (3-D) extracellular matrix (ECM) barriers dominated by type I collagen or fibrin. Based largely on analyses of its impact on cell function under two-dimensional culture conditions, MT1-MMP is categorized as a multifunctional molecule with 1) a structurally distinct, N-terminal catalytic domain; 2) a C-terminal hemopexin domain that regulates substrate recognition as well as conformation; and 3) a type I transmembrane domain whose cytosolic tail controls protease trafficking and signaling cascades. The MT1-MMP domains that subserve cell trafficking through 3-D ECM barriers in vitro or in vivo, however, remain largely undefined. Herein, we demonstrate that collagen-invasive activity is not confined strictly to the catalytic, hemopexin, transmembrane, or cytosolic domain sequences of MT1-MMP. Indeed, even a secreted collagenase supports invasion when tethered to the cell surface in the absence of the MT1-MMP hemopexin, transmembrane, and cytosolic tail domains. By contrast, the ability of MT1-MMP to support fibrin-invasive activity diverges from collagenolytic potential, and alternatively, it requires the specific participation of MT-MMP catalytic and hemopexin domains. Hence, the tissue-invasive properties of MT1-MMP are unexpectedly embedded within distinct, but parsimonious, sequences that serve to tether the requisite matrix-degradative activity to the surface of migrating cells.

scholarly journals Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2916-2923 ◽  
Author(s):  
Laura Genís ◽  
Pilar Gonzalo ◽  
Antonio S. Tutor ◽  
Beatriz G. Gálvez ◽  
Antonio Martínez-Ruiz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Tube Formation ◽  
Type I ◽  
Endothelial Migration ◽  
Membrane Type

Abstract Nitric oxide (NO) is essential for vascular homeostasis and is also a critical modulator of angiogenesis; however, the molecular mechanisms of NO action during angiogenesis remain elusive. We have investigated the potential relationship between NO and membrane type 1–matrix metalloproteinase (MT1-MMP) during endothelial migration and capillary tube formation. Endothelial NO synthase (eNOS) colocalizes with MT1-MMP at motility-associated structures in migratory human endothelial cells (ECs); moreover, NO is produced at these structures and is released into the medium during EC migration. We have therefore addressed 2 questions: (1) the putative regulation of MT1-MMP by NO in migratory ECs; and (2) the requirement for MT1-MMP in NO-induced EC migration and tube formation. NO upregulates MT1-MMP membrane clustering on migratory human ECs, and this is accompanied by increased degradation of type I collagen substrate. MT1-MMP membrane expression and localization are impaired in lung ECs from eNOS-deficient mice, and these cells also show impaired migration and tube formation in vitro. Inhibition of MT1-MMP with a neutralizing antibody impairs NOinduced tube formation by human ECs, and NO-induced endothelial migration and tube formation are impaired in lung ECs from mice deficient in MT1-MMP. MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders.

scholarly journals Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

2006 ◽  
Vol 282 (7) ◽  
pp. 4924-4931 ◽  
Author(s):  
Maria V. Barbolina ◽  
Brian P. Adley ◽  
Edgardo V. Ariztia ◽  
Yueying Liu ◽  
M. Sharon Stack
Keyword(s):  
Matrix Metalloproteinase ◽  
Ovarian Carcinoma ◽  
Three Dimensional ◽  
Carcinoma Cells ◽  
Collagenolytic Activity ◽  
Type I ◽  
Collagen Gels ◽  
Ovarian Carcinoma Cells ◽  
Membrane Type

Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, and collagen-induced integrin clustering up-regulates the expression of the transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity is important in intraperitoneal metastasis, potentiating invasion through the mesothelial cell layer and colonization of the submesothelial collagen-rich matrix. The objective of this study was to elucidate a potential mechanistic link between collagen adhesion and MT1-MMP expression. Our results indicate that culturing cells on three-dimensional collagen gels, but not thin layer collagen or synthetic threedimensional hydrogels, results in rapid induction of the transcription factor EGR1. Integrin signaling through a SRC kinase-dependent pathway is necessary for EGR1 induction. Silencing of EGR1 expression using small interfering RNA abrogated collagen-induced MT1-MMP expression and inhibited cellular invasion of three-dimensional collagen gels. These data support a model for intraperitoneal metastasis wherein collagen adhesion and clustering of collagen binding integrins activates integrin-mediated signaling via SRC kinases to induce expression of EGR1, resulting in transcriptional activation of the MT1-MMP promoter and subsequent MT1-MMP-catalyzed collagen invasion. This model highlights the role of unique interactions between ovarian carcinoma cells and interstitial collagens in the ovarian tumor microenvironment in inducing gene expression changes that potentiate intraperitoneal metastatic progression.

Hypoxic inhibition of human cardiac fibroblast invasion and MMP-2 activation may impair adaptive myocardial remodelling

2007 ◽  
Vol 35 (5) ◽  
pp. 905-907 ◽  
Author(s):  
M.E. Morley ◽  
K. Riches ◽  
C. Peers ◽  
K.E. Porter
Keyword(s):  
Type I Collagen ◽  
Cardiac Fibroblasts ◽  
Experimental Models ◽  
Matrix Metalloproteinase 2 ◽  
Type I ◽  
Proteolytic Activation ◽  
Hypoxic Conditions ◽  
Myocardial Remodelling ◽  
Membrane Type

Cardiac fibroblasts account for up to two-thirds of the total number of cells in the normal heart and are responsible for extracellular matrix homoeostasis. In vitro, type I collagen, the predominant myocardial collagen, stimulates proteolytic activation of constitutively secreted proMMP-2 (pro-matrix metalloproteinase-2). This occurs at the cell membrane and requires formation of a ternary complex with MT1-MMP (membrane-type-1 MMP) and TIMP-2 (tissue inhibitor of metalloproteinases-2). Following MI (myocardial infarction), normally quiescent fibroblasts initiate a wound healing response by transforming into a proliferative and invasive myofibroblast phenotype. Deprivation of oxygen to the myocardium is an inevitable consequence of MI; therefore this reparative event occurs under chronically hypoxic conditions. However, species and preparation variations can strongly influence fibroblast behaviour, which is an important consideration when selecting experimental models for provision of clinically useful information.

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