Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14)

Covington, Marisa D.; Burghardt, Robert C.; Parrish, Alan R.

doi:10.1152/ajprenal.00179.2005

Cited by 87 publications

(73 citation statements)

References 58 publications

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“…The inhibition effect of the positive compounds MMP inhibitor II and MMP inhibitor III from Merck were determined with an IC 50 value of 13.05 nM and 10.20 nM, respectively which are consistent with the references 19,20 . For optimal signal to noise ratio, we chose 10 nM cd-MMP-1 and 10 µM of the compound concentration for the initial screening assay.…”

Section: Inhibition Of Cd-mmp-1 By Flavonoidssupporting

confidence: 81%

The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors

Lü

Zhu

Zou

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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Section: Inhibition Of Cd-mmp-1 By Flavonoidssupporting

confidence: 81%

The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors

Lü

Zhu

Zou

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…31,33,43 In particular, we have shown that increased MMP expression and activity can regulate N-cadherin function through proteolytic degradation. 29,30,44 Cardiac-specific loss of N-cadherin in the heart leads to a dilated cardiomyopathy attributable to loss of the integrity of cell adhesion junctions. 45 Because of their homophilic binding and adhesive specificities, N-cadherin/catenin complex is required for cadherin-mediated cell adhesion and linkage to the actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

“…29,30 Western blot analysis of the myocardial membrane fraction in banded WT and PI3K␣DN mice showed a modest increase in N-cadherin levels ( Figure 6A and 6B), whereas in banded PI3K␥KO mice, there was a 75% loss of N-cadherin levels ( Figure 6A and 6B). In contrast, in the banded PI3K␥KO (and PI3K␣DN) mice, levels of ␤-catenin in the heart were significantly increased compared with banded WT mice ( Figure 6C).…”

Section: Specific Loss Of N-cadherin From Adhesion Complexes While ␤-mentioning

confidence: 99%

Loss of PI3Kγ Enhances cAMP-Dependent MMP Remodeling of the Myocardial N-Cadherin Adhesion Complexes and Extracellular Matrix in Response to Early Biomechanical Stress

Guo

Kassiri²,

Basu³

et al. 2010

Circulation Research

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Rationale: Mechanotransduction and the response to biomechanical stress is a fundamental response in heart disease. Loss of phosphoinositide 3-kinase (PI3K)␥, the isoform linked to G protein-coupled receptor signaling, results in increased myocardial contractility, but the response to pressure overload is controversial. Objective:To characterize molecular and cellular responses of the PI3K␥ knockout (KO) mice to biomechanical stress. Methods and Results:In response to pressure overload, PI3K␥KO mice deteriorated at an accelerated rate compared with wild-type mice despite increased basal myocardial contractility. These functional responses were associated with compromised phosphorylation of Akt and GSK-3␣. In contrast, isolated single cardiomyocytes from banded PI3K␥KO mice maintained their hypercontractility, suggesting compromised interaction with the extracellular matrix as the primary defect in the banded PI3K␥KO mice. ␤-Adrenergic stimulation increased cAMP levels with increased phosphorylation of CREB, leading to increased expression of cAMP-responsive matrix metalloproteinases (MMPs), MMP2, MT1-MMP, and MMP13 in cardiomyocytes and cardiofibroblasts. Loss of PI3K␥ resulted in increased cAMP levels with increased expression of MMP2, MT1-MMP, and MMP13 and increased MMP2 activation and collagenase activity in response to biomechanical stress. Selective loss of N-cadherin from the adhesion complexes in the PI3K␥KO mice resulted in reduced cell adhesion. The ␤-blocker propranolol prevented the upregulation of MMPs, whereas MMP inhibition prevented the adverse remodeling with both therapies, preventing the functional deterioration in banded PI3K␥KO mice. In banded wild-type mice, long-term propranolol prevented the adverse remodeling and systolic dysfunction with preservation of the N-cadherin levels. Conclusions:The enhanced propensity to develop heart failure in the PI3K␥KO mice is attributable to a cAMP-dependent upregulation of MMP expression and activity and disorganization of the N-cadherin/␤-catenin cell adhesion complex. ␤-Blocker therapy prevents these changes thereby providing a novel mechanism of action for these drugs. (Circ Res. 2010;107:1275-1289.)

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“…Cleavage of E-cadherin and shedding of an 80-kD fragment can be mediated by matrilysin, stromelysin-1, 5,6 plasmin 7 and a disintegrin and metalloproteinase 10 (ADAM10). 8 For N-cadherin, a 90-kD fragment can be released by the enzymes matrix metalloproteinase (MMP), 9 plasmin, 10 ADAM10, 11 membrane type 1-MMP (MT1-MMP) 12 and MT5-MMP. 13 Soluble E-cadherin (sE-CAD) has been described in the circulation of cancer patients.…”

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confidence: 99%

Soluble N‐cadherin in human biological fluids

Derycke

Wever

Stove

et al. 2006

Intl Journal of Cancer

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Classical cadherins such as E-, P-and N-cadherin are transmembrane proteins that mediate cell-cell adhesion, and are important in embryogenesis, maintenance of tissue integrity and cancer. Proteolytic shedding of the extracellular domain results in the generation of soluble E-, P-or N-cadherin ectodomains. Circulating soluble E-and P-cadherin have been described in the serum, and elevated levels were detected in cancer patients when compared with healthy persons. Here we report the presence of soluble N-cadherin, a 90-kD protein fragment, in the serum of both healthy persons and cancer patients, using a direct ELISA and immunoprecipitation. A correlation was found between prostate specific antigen and soluble N-cadherin, and significantly elevated levels were detected in prostate cancer follow-up patients. The Ncadherin protein is neo-expressed by carcinomas of the prostate, and is responsible for epithelial to fibroblastic transition. This is reflected by the higher concentrations of soluble N-cadherin in prostate cancer patients than in healthy persons. ' 2006 Wiley-Liss, Inc.Key words: soluble N-cadherin; serum; cancer Cell-cell adhesion molecules play an important role during embryogenesis, tumor invasion and metastasis. The cadherins, Ca 21 -dependent cell-cell adhesion molecules, are essential for intercellular connections. E (epithelial)-cadherin is involved in normal epithelial cell-cell interactions, but is often downregulated in epithelioid cancer cells. These cancer cells can switch cadherin expression from E-to N-(neural), 1 E-to P-(placental) 2 or E-to OB-(osteoblast)-cadherin.3 This coincides with the transition from an epithelioid to a fibroblastic phenotype, and is often correlated with invasiveness. 4 Proteolysis can contribute to the impairment of the cadherin function. Several enzymes have been shown to be responsible for the shedding of the extracellular domain. Cleavage of E-cadherin and shedding of an 80-kD fragment can be mediated by matrilysin, stromelysin-1, 5,6 plasmin 7 and a disintegrin and metalloproteinase 10 (ADAM10).8 For N-cadherin, a 90-kD fragment can be released by the enzymes matrix metalloproteinase (MMP), 9 plasmin, 10 ADAM10, 11 membrane type 1-MMP (MT1-MMP) 12 and MT5-MMP. 13Soluble E-cadherin (sE-CAD) has been described in the circulation of cancer patients.14 In that study, the mean sE-CAD level, detected by enzyme linked immunosorbent assay (ELISA), in serum was significantly higher in the studied cancer patients (3.8 6 2.36 lg/ml) when compared with the healthy controls (1.99 6 0.5 lg/ml). In addition, sE-CAD was detected in serum of patients with diabetes or hepatitis, but these values were not significantly different from the healthy controls. As a result, sE-CAD is now propagated as a marker for early prediction of tumor recurrence of gastric cancer.15 sE-CAD is also found in urine 16 and the mean levels in the urine of patients with bladder cancer are significantly higher than in the urine of healthy persons (1.6 vs. 0.9 lg/ml). 17High levels of sE-CAD appear to ...

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Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14)

Cited by 87 publications

References 58 publications

The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors

The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors

Loss of PI3Kγ Enhances cAMP-Dependent MMP Remodeling of the Myocardial N-Cadherin Adhesion Complexes and Extracellular Matrix in Response to Early Biomechanical Stress

Soluble N‐cadherin in human biological fluids

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