scholarly journals LPS Counter Regulates RNA Expression of Extracellular Proteases and Their Inhibitors in Murine Macrophages

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Andreas Hald ◽  
Birgitte Rønø ◽  
Leif R. Lund ◽  
Kristoffer L. Egerod
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Serine Proteases ◽  
Gene Expression Regulation ◽  
Proteolytic Enzymes ◽  
Matrix Degradation ◽  
Extracellular Proteases ◽  
The Matrix ◽  
Matrix Metabolism ◽  
Temporal Expression Pattern

Besides their evident importance in host defense, macrophages have been shown to play a detrimental role in different pathological conditions, including chronic inflammation, atherosclerosis, and cancer. Regardless of the exact situation, macrophage activation and migration are intimately connected to extracellular matrix degradation. This process is accomplished by multiple proteolytic enzymes, including serine proteases and members of the matrix metalloproteinase family. In this study, we have utilized qPCR arrays to simultaneously analyze the temporal expression pattern of a range of genes involved in extracellular matrix metabolism in the mouse derived-macrophage cell line RAW 264.7 following stimulation with LPS. Our results revealed that LPS induces the expression of matrix metalloproteinases while at the same time decreased the expression of matrix metalloproteinase inhibitors. The opposite scenario was found for the genes encoding serine proteases, which were downregulated while their inhibitors were upregulated. In addition, intergenic comparison of the expression levels of related proteases revealed large differences in their basal expression level. These data highlight the complexity of the gene expression regulation implicated in macrophage-dependent matrix degradation and furthermore emphasize the value of qPCR array techniques for the investigation of the complex regulation of the matrix degradome.

scholarly journals Matrix Metalloproteinases in Cerebrovascular Disease

1998 ◽  
Vol 18 (11) ◽  
pp. 1163-1172 ◽  
Author(s):  
Sheila Mun-Bryce ◽  
Gary A. Rosenberg
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Serine Proteases ◽  
Capillary Permeability ◽  
Proteolytic Enzymes ◽  
Cellular Damage ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Intracerebral Injection ◽  
Type Iv Collagenase ◽  
The Matrix

Cerebral ischemia and intracerebral hemorrhage cause extensive damage to neurons, disrupt the extracellular matrix, and increase capillary permeability. Multiple substrates participate in the cellular damage, including free radicals and proteases. Matrix metalloproteinases and serine proteases are two classes of proteases that are normally present in brain in latent forms, but once activated, contribute to the injury process. These enzymes have a unique role in the remodeling of the extracellular matrix and in the modulation of the capillary permeability. Intracerebral injection of the matrix metalloproteinase, type IV collagenase, attacks the basal lamina around the capillary and opens the blood—brain barrier, Extracellular matrix-degrading proteases are induced by immediate early genes and cytokines, and regulated by growth factors. Activity of the matrix metalloproteinases is tightly controlled by activation mechanisms and tissue inhibitors of metalloproteinases. During ischemia and hemorrhage, multiple matrix metalloproteinases and serine proteases are produced along with their inhibitors. These proteolytic enzymes are involved in the delayed injury that accompanies the neuroinflammatory response. Synthetic inhibitors to metalloproteinases reduce proteolytic tissue damage, and may limit secondary neuroinflammation.

Some characteristics of extracellular proteases produced by members of the Chytridiales and the Spizellomycetales (Chytridiomycetes)

1994 ◽  
Vol 40 (2) ◽  
pp. 106-112 ◽  
Author(s):  
Thomas Krarup ◽  
Lauritz W. Olson ◽  
Hans Peter Heldt-Hansen
Keyword(s):  
Proteolytic Activity ◽  
Isoelectric Focusing ◽  
Serine Proteases ◽  
Proteolytic Enzymes ◽  
Complex Compounds ◽  
Extracellular Proteases ◽  
Peptide Substrates ◽  
Proteolytic Activities ◽  
Selection Of

The extracellular proteolytic enzymes of eight saprophytic, eucarpic, and monocentric isolates from two genera of the order Spizellomycetales and from one genus of the order Chytridiales (Chytridiomycetes) have been partially characterized. The isolectric points of the proteases were estimated from zymograms and demonstrate the existence of three types of proteolytic activity in most isolates. The proteases were tested against synthetic chromogenic peptide substrates and a selection of cations and more complex compounds, and the results suggest that parts of the extracellular proteolytic activities are due to proteases from two groups: the Ca2+ stabilized proteases and the alkaline serine proteases.Key words: serine proteases, metalloproteases, Chytridiomycetes, isoelectric focusing, chromogenic peptide substrates.

scholarly journals Colchicine causes increased matrix metalloproteinase expression and extracellular matrix degradation in hydra

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Xiaoming Zhang Zhang ◽  
Roland Aufschnaiter ◽  
Li Li ◽  
Matthews Athiyal ◽  
Fengzhen Ren ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation

Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 447-456 ◽  
Author(s):  
O. Behrendtsen ◽  
C.M. Alexander ◽  
Z. Werb
Keyword(s):  
Extracellular Matrix ◽  
Giant Cells ◽  
Matrix Degradation ◽  
Trophoblast Cells ◽  
Type Iv Collagenase ◽  
Type Iv ◽  
The Matrix ◽  
Remodeling Of Extracellular Matrix ◽  
Trophoblast Giant Cells ◽  
Blocking Antibodies

The maintenance and developmental remodeling of extracellular matrix is crucial to such processes as uterine implantation and the cell migratory events of morphogenesis. When mouse blastocysts are placed in culture they adhere to extracellular matrix, and trophoblast giant cells migrate out onto the matrix and degrade it. The secretion of functional proteinases by developing mouse embryos increases dramatically at the time of implantation. By zymography we identified the major secreted gelatin-degrading proteinase, also known as type IV collagenase, as one migrating at 92 × 10(3) Mr. Several casein-degrading proteinases were also secreted. The tissue inhibitor of metalloproteinases (TIMP) inhibited all of the embryo-derived proteinases detected by gelatin gel zymography, indicating that they are metalloproteinases, whereas TIMP did not inhibit all of the caseinases. Urokinase was also secreted. Addition of TIMP at 5–500 nM effectively inhibited the degradation of matrix by the trophoblast outgrowths. Blocking antibodies directed against 92 × 10(3) Mr gelatinase abolished matrix degradation by the trophoblast cells. These observations suggest that several metalloproteinases are regulated in early development and that 92 × 10(3) Mr gelatinase, in particular, has a rate-limiting function in degradation of the maternal extracellular matrix by trophoblast cells.

scholarly journals Extracellular Matrix Degradation and Tissue Remodeling in Periprosthetic Loosening and Osteolysis: Focus on Matrix Metalloproteinases, Their Endogenous Tissue Inhibitors, and the Proteasome

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Spyros A. Syggelos ◽  
Alexios J. Aletras ◽  
Ioanna Smirlaki ◽  
Spyros S. Skandalis
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Molecular Mechanisms ◽  
Total Joint Replacement ◽  
Proteolytic Enzymes ◽  
Tissue Remodeling ◽  
Wear Particle ◽  
Matrix Degradation ◽  
Tissue Inhibitors ◽  
Extracellular Matrix Degradation

The leading complication of total joint replacement is periprosthetic osteolysis, which often results in aseptic loosening of the implant, leading to revision surgery. Extracellular matrix degradation and connective tissue remodeling around implants have been considered as major biological events in the periprosthetic loosening. Critical mediators of wear particle-induced inflammatory osteolysis released by periprosthetic synovial cells (mainly macrophages) are inflammatory cytokines, chemokines, and proteolytic enzymes, mainly matrix metalloproteinases (MMPs). Numerous studies reveal a strong interdependence of MMP expression and activity with the molecular mechanisms that control the composition and turnover of periprosthetic matrices. MMPs can either actively modulate or be modulated by the molecular mechanisms that determine the debris-induced remodeling of the periprosthetic microenvironment. In the present study, the molecular mechanisms that control the composition, turnover, and activity of matrix macromolecules within the periprosthetic microenvironment exposed to wear debris are summarized and presented. Special emphasis is given to MMPs and their endogenous tissue inhibitors (TIMPs), as well as to the proteasome pathway, which appears to be an elegant molecular regulator of specific matrix macromolecules (including specific MMPs and TIMPs). Furthermore, strong rationale for potential clinical applications of the described molecular mechanisms to the treatment of periprosthetic loosening and osteolysis is provided.

scholarly journals Protease–Antiprotease Imbalance in Bronchiectasis

2021 ◽  
Vol 22 (11) ◽  
pp. 5996
Author(s):  
Martina Oriano ◽  
Francesco Amati ◽  
Andrea Gramegna ◽  
Anthony De Soyza ◽  
Marco Mantero ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Disease Severity ◽  
Neutrophil Elastase ◽  
Proteinase Inhibitor ◽  
Serine Proteases ◽  
Matrix Degradation ◽  
Long Term Outcomes ◽  
Elastase Activity ◽  
Severe Deficiency

Airway inflammation plays a central role in bronchiectasis. Protease–antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases’ over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease–antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.

scholarly journals Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiangtao Wan ◽  
Guowei Zhang ◽  
Xin Li ◽  
Xianshuai Qiu ◽  
Jun Ouyang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Differentiation ◽  
Matrix Metalloproteinase ◽  
Biological Activities ◽  
Expression Profiles ◽  
Morphological Characteristics ◽  
Point Of View ◽  
Matrix Metalloproteinase 3 ◽  
Degradation Reactions ◽  
The Matrix

Cells must alter their expression profiles and morphological characteristics but also reshape the extracellular matrix (ECM) to fulfill their functions throughout their lifespan. Matrix metalloproteinase 3 (MMP-3) is a member of the matrix metalloproteinase (MMP) family, which can degrade multiple ECM components. MMP-3 can activate multiple pro-MMPs and thus initiates the MMP-mediated degradation reactions. In this review, we summarized the function of MMP-3 and discussed its effects on biological activities. From this point of view, we emphasized the positive and negative roles of MMP-3 in the pathogenesis of disease and cell differentiation, highlighting that MMP-3 is especially closely involved in the occurrence and development of osteoarthritis. Then, we discussed some pathways that were shown to regulate MMP-3. By writing this review, we hope to provide new topics of interest for researchers and attract more researchers to investigate MMP-3.

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