scholarly journals Deafferentation-Induced Redistribution of MMP-2, but Not of MMP-9, Depends on the Emergence of GAP-43 Positive Axons in the Adult Rat Cochlear Nucleus

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Michaela Fredrich ◽  
Robert-Benjamin Illing
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Cochlear Nucleus ◽  
Ecm Remodeling ◽  
Adult Rat ◽  
Anteroventral Cochlear Nucleus ◽  
The Matrix ◽  
Ventral Nucleus ◽  
Induced Changes ◽  
Trapezoid Body

The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM), were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN) following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB) prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43) into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

scholarly journals Glia-related mechanisms in the anteroventral cochlear nucleus of the adult rat in response to unilateral conductive hearing loss

2014 ◽  
Vol 8 ◽  
Author(s):  
Verónica Fuentes-Santamaría ◽  
Juan C. Alvarado ◽  
Diego F. López-Muñoz ◽  
Pedro Melgar-Rojas ◽  
María C. Gabaldón-Ull ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Nucleus ◽  
Conductive Hearing Loss ◽  
Adult Rat ◽  
Anteroventral Cochlear Nucleus ◽  
Conductive Hearing

scholarly journals The Unwounded Skin Remodeling in Animal Models of Diabetes Types 1 and 2

2013 ◽  
pp. 519-526 ◽  
Author(s):  
M. KNAŚ ◽  
M. NICZYPORUK ◽  
A. ZALEWSKA ◽  
H. CAR
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Diabetes Type ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Control Group ◽  
Diabetes Type 1 ◽  
Tissue Inhibitors ◽  
The Matrix

Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health complications, including dermatologic problems. The diabetic skin is characterized by disturbances in collagen metabolism. A tissue remodeling depends on the degradation of extracellular matrix through the matrix metalloproteinases, which are regulated by e.g. the tissue inhibitors of metalloproteinases. The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The aim of this study was to determine the concentration of metalloproteinase 2, tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1 in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1 concentrations in the skin as compared to the untreated diabetic skin. The concentrations of MMP2 in the skin of treated rats did not show significant differences from the healthy control group. TIMP3 concentrations in the skin of treated rats are not returned to the level observed in the control group. Disturbances of the extracellular matrix of the skin are similar in diabetes type 1 and 2. Application of insulin in diabetes therapy more preferably affects the extracellular matrix homeostasis of the skin.

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.

Enhancement of neural synchronization in the anteroventral cochlear nucleus. II. Responses in the tuning curve tail

1994 ◽  
Vol 71 (3) ◽  
pp. 1037-1051 ◽  
Author(s):  
P. X. Joris ◽  
P. H. Smith ◽  
T. C. Yin
Keyword(s):  
Cochlear Nucleus ◽  
Tuning Curve ◽  
Phase Locking ◽  
Low Frequency ◽  
Companion Paper ◽  
Acoustic Stimuli ◽  
Anteroventral Cochlear Nucleus ◽  
Temporal Features ◽  
Peripheral Auditory System ◽  
Trapezoid Body

1. Discharges of neurons in the peripheral auditory system contain information about the temporal features of acoustic stimuli. Phase-locking of neurons in the anteroventral cochlear nucleus (AVCN) is usually reported to be less robust than in auditory nerve (AN) fibers, which provide their major input. In a companion paper we reported that some cells in AVCN of the cat show enhanced phase-locking compared with the AN when stimulated at the frequency to which they are most sensitive [characteristic frequency (CF)]. We called neurons "high-sync" when they showed vector strengths (R, a measure of phase-locking) > or = 0.9. Here we report phase-locking properties to stimuli at frequencies below CF. 2. Horseradish peroxidase-filled glass micropipettes or metal microelectrodes were inserted into the trapezoid body (TB), which is the large output tract of the AVCN. Acoustically driven fibers were classified on the basis of the shape of the poststimulus time (PST) histograms to short tone bursts at CF. We then presented low-frequency tones of increasing SPL and determined the maximum R value at 500 Hz (R500) for each fiber. Using the same experimental protocol we studied phase-locking in the ANs of two animals because maximal R values at the tuning curve tail have not been reported for AN fibers. 3. Although phase-locking in AN fibers is usually assumed to be independent of CF, we found that fibers with CF > 2 kHz tended to have higher R500 values than fibers with CF < or = 2 kHz. Moreover, R500 was > or = 0.9 in 20% (42 of 196) of the fibers studied and could be as high as 0.95. This population of fibers was defined as having "high-sync tails" and consisted almost entirely of fibers with low or medium spontaneous rate. 4. High-CF TB fibers stimulated at 500 Hz showed very high phase-locking. High-sync tails (R500 > or = 0.9) were found in 41 of 70 TB fibers. For a subset of these fibers (1/3 in total: 23 of 70) phase-locking was higher than is ever observed in the AN (R500 > or = 0.95); these fibers were defined as showing synchronization "enhancement." Virtually all fibers showing synchronization enhancement had primary-like-with-notch (PLN) PST histograms. Chopper and primary-like fibers showed high-sync tails for CFs > 3 kHz. 5. Synchronization filter functions were obtained for high-CF AN fibers by determining maximum synchronization for a range of stimuli below CF.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition

1999 ◽  
Vol 162 (3) ◽  
pp. 351-359 ◽  
Author(s):  
SC Riley ◽  
R Leask ◽  
FC Denison ◽  
K Wisely ◽  
AA Calder ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Amniotic Fluid ◽  
Cell Signalling ◽  
Fetal Membranes ◽  
Tissue Inhibitors ◽  
Membrane Rupture ◽  
Specific Distribution ◽  
The Matrix ◽  
Chorion Laeve

At parturition, breakdown of extracellular matrix in the fetal membranes may play a part in the rupture of the membranes and in the aetiology of premature rupture, in addition to having a regulatory role in the cell-cell interactions and signalling at the feto-maternal interface to stimulate myometrial contractility. The matrix metalloproteinases (MMPs) are important enzymes for the breakdown of extracellular matrix and their activity is regulated by a family of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs). At parturition, alteration in the balance between MMPs and TIMPs may mediate this extracellular matrix breakdown during rupture of fetal membranes. The aims of this study were to determine if the intrauterine secretion of TIMPs changes at labour, and to characterise their cellular sources. A broad range of TIMP activities (27-30 kDa, 24 kDa and 21 kDa) were detected by reverse zymography in term amniotic fluid. There was a significant (P<0.05) decrease in the amount of TIMPs in amniotic fluid and their release with the onset of labour. The TIMPs were characterised by immunoblot as TIMPs-1, -2, -3 and -4. High levels of TIMPs were secreted by explants of chorio-decidua, decidua parietalis and placenta, with less being released by amnion. Immunolocalisation studies revealed a specific distribution pattern for each of the TIMP isoforms. Trophoblast cells of chorion laeve, decidua parietalis and placental syncytiotrophoblast demonstrated specific immunoreactivity for all four isoforms. TIMPs were also found bound to selective regions of extracellular matrix. The decrease in TIMPs during labour may permit increased breakdown of extracellular matrix in the fetal membranes and decidua at parturition, thus altering cell signalling at the feto-maternal interface and facilitating membrane rupture.

scholarly journals Role of extracellular matrix in the pathogenesis of pulmonary arterial hypertension

2018 ◽  
Vol 315 (5) ◽  
pp. H1322-H1331 ◽  
Author(s):  
Thenappan Thenappan ◽  
Stephen Y. Chan ◽  
E. Kenneth Weir
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Arterial Hypertension ◽  
Matrix Metalloproteinases ◽  
Arterial Hypertension ◽  
Proteolytic Enzymes ◽  
Disease Process ◽  
Transient Receptor Potential Channels ◽  
Ecm Remodeling ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is characterized by remodeling of the extracellular matrix (ECM) of the pulmonary arteries with increased collagen deposition, cross-linkage of collagen, and breakdown of elastic laminae. Extracellular matrix remodeling occurs due to an imbalance in the proteolytic enzymes, such as matrix metalloproteinases, elastases, and lysyl oxidases, and tissue inhibitor of matrix metalloproteinases, which, in turn, results from endothelial cell dysfunction, endothelial-to-mesenchymal transition, and inflammation. ECM remodeling and pulmonary vascular stiffness occur early in the disease process, before the onset of the increase in the intimal and medial thickness and pulmonary artery pressure, suggesting that the ECM is a cause rather than a consequence of distal pulmonary vascular remodeling. ECM remodeling and increased pulmonary arterial stiffness promote proliferation of pulmonary vascular cells (endothelial cells, smooth muscle cells, and adventitial fibroblasts) through mechanoactivation of various signaling pathways, including transcriptional cofactors YAP/TAZ, transforming growth factor-β, transient receptor potential channels, Toll-like receptor, and NF-κB. Inhibition of ECM remodeling and mechanotransduction prevents and reverses experimental pulmonary hypertension. These data support a central role for ECM remodeling in the pathogenesis of the PAH, making it an attractive novel therapeutic target.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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