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

McGuire, John K.; Li, Qinglang; Parks, William C.

doi:10.1016/s0002-9440(10)64318-0

Cited by 288 publications

(280 citation statements)

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“…23 Specifically, MMP-7 could facilitate epithelial cell migration by losing cell-cell and cell-matrix contacts. 24 To understand the biological significance of the cirrhosis-associated MMP-7 polymorphism on cell motility, a wound-healing assay was applied. HSC-T6-MMP7(Asp) cells migrated significantly faster than the HSC-T6-MMP7(Gly) and control HSC-T6-NC cells at 24 hours after wounding (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Migration of resident HSCs is believed to be critical for the progression of liver fibrosis because it accounts for the increased numbers of activated HSCs in areas of injury. 29 Moreover, MMP-7 is able to cleave ECM and basement membrane, 30 and mediate E-cadherin ectodomain shedding in injured lung epithelium, 24 leading to accelerated cell migration. In this study, the wound healing and Boyden chamber assays demonstrated that HSC-T6 cells expressing MMP-7(Asp-137) variant acquired an enhanced migratory capacity as compared with cells expressing MMP-7(Gly-137) (Fig.…”

Section: Discussionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

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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“…In a complex tissue environment, like cancer, several cell types (resident, inflammatory, tumor) express several, different MMPs, and these proteinase can either promote or restrain disease or repair processes by affecting multiple and apparently opposing processes by the same cell at the same time (Coussens et al, 2002;Egeblad and Werb, 2002;Parks et al, 2004). For example, we have determined that epithelial MMP-7 is required for wound closure and generation of antimicrobial activity (Dunsmore et al, 1998;Wilson et al, 1999) (clearly beneficial functions), but it also promotes neutrophil activation, which can be damaging and lethal McGuire et al, 2003). It is likely that to effect on different processes at the same time, a cell uses distinct mechanisms to compartmentalize an MMP to different substrates.…”

Section: Significancementioning

confidence: 97%

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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“…Epithelial cells at the edges of wounded tracheal explants migrate towards each other and fuse. MMP7 seems to mediate wound-induced epithelial migration by cleaving E-cadherin 84 . MMP7 colocalizes with E-cadherin and cleaves its extracellular domain in wounded epithelia, which results in a loosening of cell-cell attachments.…”

Section: Mmp7 Is Involved In Innate Immunity and Wound Healingmentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,560

2,180

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Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

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

Cited by 288 publications

References 50 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

Control of matrix metalloproteinase catalytic activity

Matrix metalloproteinases and the regulation of tissue remodelling

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