Matrix Metalloproteinases: Implication in Vascular Matrix Remodelling during Atherogenesis

1998 ◽  
Vol 94 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Shu Ye ◽  
Steve Humphries ◽  
Adriano Henney
Keyword(s):  
Matrix Metalloproteinases ◽  
Plaque Rupture ◽  
Matrix Deposition ◽  
Naturally Occurring ◽  
Extracellular Matrix Components ◽  
The Matrix ◽  
Preferential Binding ◽  
Artery Disease ◽  
Matrix Accumulation ◽  
Functional Analyses

1. The matrix metalloproteinases are a family of at least 16 zinc-dependent endopeptidases possessing catalytic activity against extracellular matrix components. Some members of this family have been implicated in vascular matrix remodelling in the pathogenesis of atherosclerosis. 2. A common, naturally occurring variant has been identified in the promoter of the stromelysin gene with one allele having a run of five adenosines (5A) and the other having six adenosines (6A). Functional analyses have shown that the 6A allele has a lower promoter activity than the 5A allele, which is probably attributable to preferential binding of a putative transcriptional repressor protein. 3. In patients with coronary artery disease, the 6A allele has been found to be associated with progression of atherosclerosis assessed by sequential quantitative angiography. 4. In conclusion, the matrix metalloproteinases may be over-expressed in certain locations in atherosclerotic plaques, which might contribute to local destruction of connective tissue and thus plaque rupture. In the majority of lesional areas, however, matrix synthesis is likely to outstrip matrix degradation, because matrix accumulation is a major feature of most atheromas. This imbalance favouring matrix deposition is likely to be exacerbated in individuals with the 6A6A genotype in whom stromelysin expression is lower due to the weaker stromelysin promoter.

Mechanical Loading Modulates Gene Expression in Chondrocyte-Seeded Agarose Hydrogels

2001 ◽  
Author(s):  
Sansan S. Lo ◽  
Robert L. Mauck ◽  
Sara L. Seyhan ◽  
Glyn D. Palmer ◽  
Van C. Mow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mechanical Loading ◽  
Promoter Activity ◽  
Dynamic Compression ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Matrix Deposition ◽  
Matrix Gene ◽  
The Matrix ◽  
Matrix Accumulation

Abstract A successful tissue engineered articular cartilage construct needs to possess mechanical, biochemical, and histological features similar to that of native cartilage in order to serve its load-bearing function. Agarose is a suitable scaffold material for chondrocyte cultures (1,2), allowing long-term maintenance of cell phenotype and the elaboration of a functional cartilage-like matrix. This culture system facilitates further elucidation of the roles of matrix and cell-matrix interactions in the regulation of chondrocyte response to mechanical loads. We have previously shown (3) that mechanical loading at a physiologic frequency can increase the rate of matrix deposition, increasing mechanical properties of the tissue engineered constructs (∼21 fold increases in HA over day 0 with loading vs. ∼4 fold increases for free swelling controls). We have also shown that dynamic loading of transiently transfected chondrocytes in agarose hydrogels for 1 hour at 10% strain increased aggrecan promoter activity by ∼1.5 fold (4). In this study we sought to further characterize the short term response of chondrocytes to static load (by measuring aggrecan promoter activity) and the effects of dynamic compression on aggrecan gene expression over a longer (3 day) culture period (by monitoring mRNA levels). Monitoring matrix gene expression during early times of culture, when there is little matrix accumulation and the cells deform directly with the matrix (5), may provide insights into cellular responses to strain and allow for the optimization of cartilage bioreactor conditions.

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fabrizio Luppi ◽  
Meena Kalluri ◽  
Paola Faverio ◽  
Michael Kreuter ◽  
Giovanni Ferrara
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Epidemiological Studies ◽  
Elderly Subjects ◽  
Single Individual ◽  
Negative Consequences ◽  
Management Options ◽  
Artery Disease ◽  
Matrix Accumulation

AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3–5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities.

The matrix metalloproteinases inhibitor Ro 26-2853 extends survival in transgenic ALS mice

2006 ◽  
Vol 200 (1) ◽  
pp. 166-171 ◽  
Author(s):  
Stefan Lorenzl ◽  
Sabine Narr ◽  
Barabara Angele ◽  
Hans Willi Krell ◽  
Jason Gregorio ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
The Matrix

VEGF signaling activates the matrix metalloproteinases, MmpL7 and MmpL5 at the sites of active skeletal growth and MmpL7 regulates skeletal elongation

2021 ◽  
Vol 473 ◽  
pp. 80-89
Author(s):  
Miri Morgulis ◽  
Mark R. Winter ◽  
Ligal Shternhell ◽  
Tsvia Gildor ◽  
Smadar Ben-Tabou de-Leon
Keyword(s):  
Matrix Metalloproteinases ◽  
Skeletal Growth ◽  
Vegf Signaling ◽  
The Matrix

Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9

1997 ◽  
Vol 33 (10) ◽  
pp. 1685-1692 ◽  
Author(s):  
A. Vacca ◽  
S. Moretti ◽  
D. Ribatti ◽  
A. Pellegrino ◽  
N. Pimpinelli ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Mycosis Fungoides ◽  
The Matrix

scholarly journals Protein kinase C regulates the recruitment of syndecan-4 into focal contacts.

1995 ◽  
Vol 6 (11) ◽  
pp. 1503-1513 ◽  
Author(s):  
P C Baciu ◽  
P F Goetinck
Keyword(s):  
Protein Kinase C ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Matrix Deposition ◽  
Kinase C ◽  
Focal Contacts ◽  
The Matrix ◽  
Migratory Cells

Cell surface heparan sulfate proteoglycans have been implicated as co-receptors facilitating cell adhesion and growth factor binding. Recent studies on the role of a family of transmembrane heparan sulfate proteoglycans, syndecans, in cell adhesion has identified one member, syndecan-4, to be present within focal contacts. The current study investigates the mechanisms regulating the association of syndecan-4 with focal contacts based upon its immunolocalization with vinculin in quiescent, serum-stimulated, and 12-0-tetradecanoylphorbol 13-acetate (TPA)-induced cultures. In quiescent cells, syndecan-4 did not localize to focal contacts. However, activation of protein kinase C by TPA or serum induces the active recruitment of syndecan-4 into focal contacts. This induction preferentially localizes syndecan-4 to focal contacts behind the leading lamella, the subnuclear region, and along the trailing edge of migratory cells. Focal contacts in either freshly adhered cells or in the leading lamellae of migrating cells did not stain for syndecan-4. In addition to the observed subcellular distribution and recruitment, syndecan-4 was observed to co-localize with endogenously synthesized fibronectin fibrils within focal contacts as well as with fibrils present in the matrix. These findings suggest that protein kinase C activation results in syndecan-4 recruitment to focal contacts and its association with sites of matrix deposition.

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