Heparan Sulfate Proteoglycans as Extracellular Docking Molecules for Matrilysin (Matrix Metalloproteinase 7)

Yu, Winston; Woessner, Jeff

doi:10.1074/jbc.275.6.4183

Cited by 218 publications

(203 citation statements)

References 53 publications

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“…These include CD44 heparan sulfate proteoglycan (HSPG), cholesterol sulfate, and CD151. [18][19][20] Cholesterol sulfate is a component of lipid raft and CD151 is a transmembrane 4 superfamily protein that appears in a detergent-insoluble lipid-containing microdomain. To learn the possible docking mechanism of MMP-7, the behavior of the membrane-associated MMP-7(Asp-137) variant was analyzed in the presence of detergent.…”

Section: Resultsmentioning

confidence: 99%

A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis

Hung

Chang

et al. 2009

Hepatology

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Liver cirrhosis is characterized by progressive accumulation of extracellular matrix following chronic liver injuries. In the extracellular space, the constant turnover of liver matrix is regulated by the matrix metalloproteinase (MMP) class of enzyme. To assess whether genetic variations in MMP would result in diversity of liver cirrhosis, a case-control study of 320 patients with hepatocellular carcinoma, with or without cirrhosis, was conducted. Ten single-nucleotide polymorphism markers from four potential fibrosis-associated genes were selected for genotyping. Among these genes, a nonsynonymous single-nucleotide polymorphism which generates the variation of Gly-137 and Asp-137 in the MMP-7 gene was found to be strongly associated with the development of liver cirrhosis. In contrast to MMP-7(Gly-137) that predominantly secretes out into the cell culture medium, the cirrhosis-associated MMP-7(Asp-137) variant is preferentially localized on the extracellular membranes where it exerts its proteolytic activity on pericellular substrates. Functional analysis demonstrated an increased ability of the MMP-7(Asp-137) variant to associate with the cell surface CD151 molecule. In wound-healing and Boyden chamber assays, cell motility was specifically enhanced with the expression of MMP-7(Asp-137) as compared to the cells expressing MMP-7(Gly-137). These results demonstrate that the MMP-7(Asp-137) variant confers a gain-of-function phenotype for MMP-7. Conclusion: We have identified a novel genetic association of MMP-7(Asp-137) variant with liver cirrhosis in patients with hepatocellular carcinoma. Whether the MMP-7 variant can be a new marker for liver cirrhosis will be further studied.

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Section: Resultsmentioning

confidence: 99%

A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis

Hung

Chang

et al. 2009

Hepatology

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“…to the integrin ␣ 5 ␤ 3 , 44 gelatinase B (MMP-9) to CD44, 45 and matrilysin to surface heparan sulfate proteoglycans, 46,47 or by localized co-expression, such as the packaging of matrilysin with its prodefensin substrate in Paneth cell granules. 28 Likewise, we found that matrilysin was secreted specifically to locations of E-cadherin redistribution in migrating epithelium at the edge of mucosal wounds.…”

Section: Discussionmentioning

confidence: 99%

Matrilysin (Matrix Metalloproteinase-7) Mediates E-Cadherin Ectodomain Shedding in Injured Lung Epithelium

McGuire

Parks

2003

The American Journal of Pathology

288

264

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Matrilysin (matrix metalloproteinase-7) is highly expressed in lungs of patients with pulmonary fibrosis and other conditions associated with airway and alveolar injury. Although matrilysin is required for closure of epithelial wounds ex vivo, the mechanism of its action in repair is unknown. We demonstrate that matrilysin mediates shedding of E-cadherin ectodomain from injured lung epithelium both in vitro and in vivo. In alveolar-like epithelial cells, transfection of activated matrilysin resulted in shedding of E-cadherin and accelerated cell migration. In vivo, matrilysin co-localized with E-cadherin at the basolateral surfaces of migrating tracheal epithelium, and the reorganization of cell-cell junctions seen in wild-type injured tissue was absent in matrilysin-null samples. E-cadherin ectodomain was shed into the bronchoalveolar lavage fluid of bleomycin-injured wild-type mice, but was not shed in matrilysin-null mice. These findings identify E-cadherin as a novel substrate for matrilysin and indicate that shedding of E-cadherin ectodomain is required for epithelial repair.

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“…Rather, proteinases, such as MMPs, would likely be anchored to the cell membrane, thereby maintaining a locally high enzyme concentration and targeting their catalytic activity to specific substrates within the pericellular space. In addition to the membrane-bound MMPs, several examples of specific cell-MMP interactions have been reported, such as the binding of MMP-2 to the α v β 3 integrin (Brooks et al, 1996), MMP-1 to the α 2 β 1 integrin Stricker et al, 2001), MMP-9 to CD44 (Yu and Stamenkovic, 2000), and MMP-7 to surface proteoglycans (Yu and Woessner, 2000;Yu et al, 2002), cholesterol (Yamamoto et al, 2006), and CD151 (Shiomi et al, 2005). As suggested for CD44 (Yu and Stamenkovic, 2000) and the α 2 β 1 integrin ), these membrane anchors may act as accessory factors that mediate both pro-enzyme activation and binding of both substrate and proteinase, thereby increasing the probability of proteolysis (Fig.…”

Section: Compartmentalizationmentioning

confidence: 99%

Control of matrix metalloproteinase catalytic activity

2007

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SummaryAs their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function in vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.

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Heparan Sulfate Proteoglycans as Extracellular Docking Molecules for Matrilysin (Matrix Metalloproteinase 7)

Cited by 218 publications

References 53 publications

A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis

A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis

Matrilysin (Matrix Metalloproteinase-7) Mediates E-Cadherin Ectodomain Shedding in Injured Lung Epithelium

Control of matrix metalloproteinase catalytic activity

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