SEARCH · PubMed Health

Results for “Extracellular Matrix”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed1986

Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.

We have examined whether the extracellular matrix is a biochemical target for transforming growth factor-beta (TGFbeta). We find that TGFbeta increases the expression of the major extracellular matrix proteins, fibronectin and collagen. This effect is a general response to TGFbeta seen in primary cultures and established lines of cells from various types, normal and transformed. The relative incorporation of fibronectin and collagen into the matrix also increases in response to TGFbeta. The effect of TGFbeta on fibronectin levels as characterized in chick embryo fibroblasts is rapid, selective, persistent, and specific, and involves transcriptional events; it is not mimicked by other growth factors tested. The induction of anchorage-independent growth of normal fibroblasts by TGFbeta is mimicked by fibronectin and is specifically blocked by inhibitors of fibronectin binding to its cell surface receptor. The results demonstrate a functional involvement of fibronectin in mediating cellular responses to TGFbeta, and suggest a model for TGFbeta action based on the control of the extracellular matrix in target cells.

Animals↗

PubMed2003

Functional structure and composition of the extracellular matrix.

In this brief introductory paper the general structure and the molecular composition of the extracellular matrix are outlined. Ultrastructural morphology of the extracellular matrix is introduced and subsequently the molecular structure of each of the main protein families, which together make up the extracellular matrix, is reviewed. Collagens, laminins, tenascins, and proteoglycans are addressed. An important common feature is the domain structure of these in general very large proteins. Several families have domains in common, which favours extensive interactions. Integrins play an important role in these interactions and also in the communication between cells and the matrix. The extracellular matrix appears to be a very dynamic structure, which has a prominent role in normal development as well as in a variety of disease processes. Matrix metalloproteinases are essential actors in this complex interplay between cells and the extracellular matrix.

Collagen↗

PubMed1991

Increased synthesis of extracellular matrix in mesangial proliferative nephritis.

Extracellular matrix expansion is frequently noted in mesangioproliferative renal diseases. This study investigates the role of immunologic factors in glomerular matrix accumulation. The gene expression of type I and IV collagen, laminin and s-laminin was examined in the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Northern analysis was performed on glomerular RNA isolated one, three and five days after disease induction and at day 3 following prior complement depletion. Tissue was immunostained for the protein products of these genes as well as for heparan sulfate proteoglycan, entactin and PCNA (a marker of cell proliferation) at days 1, 3, 5, 14, 21 and 42. A seven- to ten-fold increase of collagen IV and laminin mRNA as well as de novo expression of collagen I mRNA occurred at days 3 and 5 corresponding to the time of maximal proliferation. S-laminin mRNA levels only increased three-fold. With the exception of s-laminin, mesangial staining for all examined matrix proteins increased to a maximum at day 5 and decreased thereafter. Focal alterations of the glomerular architecture and matrix persisted at day 42. Complement depletion prevented the histological abnormalities as well as the increased expression of matrix proteins at day 3. These findings indicate that immunologic injury in the mesangium may result in overproduction of extracellular matrix components and may ultimately contribute to the development of glomerulosclerosis.

Animals↗

PubMed1995

Osteopontin and the bone remodeling sequence. Colloidal-gold immunocytochemistry of an interfacial extracellular matrix protein.

Relative to other noncollagenous, extracellular matrix proteins in mineralized tissues, colloidal-gold immunocytochemistry has demonstrated that the ultrastructural distribution of osteopontin (OPN) is unique in that this protein preferentially accumulates at mineralized tissue interfaces. In bone, this protein is present as a major component of cell-matrix and matrix-matrix interfacial structures called cement lines and laminae limitantes. In the present article, the implications of this distinct tissue distribution are discussed in terms of the bone remodeling sequence, and a detailed account of the secretion, accumulation and potential role of OPN is presented and related to current theory on the cellular and extracellular matrix events associated with basic multicellular unit (BMU)-based bone remodeling. In this context, a proposal is made describing the production of this protein as one of the earliest, and latest, secretory activities of the osteoblastic lineage, and that this activity manifests itself morphologically as a cement line ('plane') and a lamina limitans, respectively, at bone matrix interfaces. When integrated with other, known functional characteristics of this protein, the present morphological and compositional data indicate that OPN in cement lines and laminae limitantes may participate in initial and late extracellular matrix organization and mineralization, matrix-matrix/mineral adhesion and/or cell adhesion at bone interfaces.

Animals↗

PubMedDate not supplied

Presynaptic neurones may contribute a unique glycoprotein to the extracellular matrix at the synapse.

As the extracellular matrix at the original site of a neuromuscular junction seems to play a major part in the specificity of synaptic regeneration, considerable attention has been paid to unique molecules localized to this region. Here we describe an extracellular matrix glycoprotein of the elasmobranch electric organ that is localized near the nerve endings. By immunological criteria, it is synthesized in the cell bodies, transported down the axons and is related to a glycoprotein in the synaptic vesicles of the neurones that innervate the electric organ. It is apparently specific for these neurones, as it cannot be detected elsewhere in the nervous system of the fish. Therefore, neurones seem to contribute unique extracellular matrix glycoproteins to the synaptic region. Synaptic vesicles could be involved in transporting these glycoproteins to or from the nerve terminal surface.

Animals↗

PubMed1995

The extracellular matrix during heart development.

The embryonic extracellular matrix, which is comprised of glycosaminoglycans, glycoproteins, collagens, and proteoglycans, is believed to play multiple roles during heart morphogenesis. Some of these ECM components appear throughout development, however, certain molecules exhibit an interesting transient spatial and temporal distribution. Due to significant new data that have been gathered predominantly in the past 10 years, a comprehensive review of the literature is needed. The intent of this review is to highlight work that addresses mechanisms by which extracellular matrix influences vertebrate heart development.

Animals↗

PubMed2000

Further evidence for secretion of matrix metalloproteinase-1 by Meckel's chondrocytes during degradation of the extracellular matrix.

We examined the possibility that chondrocytes in Meckel's cartilage might secrete matrix metalloproteinase-1 (MMP-1) during degradation of the extracellular matrix. Evidence for the secretion of MMP-1 was obtained by immunohistochemical staining and immunoelectron microscopy, in addition to general histochemical staining for proteoglycans. Not only staining with toluidine blue and alcian blue but also immunostaining for chondroitin sulfate proteoglycan (CSPG) revealed that levels of glycoproteins are rapidly reduced at the late stage of degradation. MMP-1 was detected continuously in cells from chondrocytes at the early stage to hypertrophic chondrocytes at the late stage. Immunoelectron microscopy revealed that the deposition of colloidal golds shifted from an intracellular localization in chondrocytes at the early stage to pericellular spaces at the late stage. The localization of tissue inhibitor of the metalloproteinase-1 (TIMP-1) at the early stage was similar to that of MMP-1, but the level of TIMP-1 decreased significantly in hypertrophic cartilage. These findings suggest that MMP-1 is present continuously in Meckel's chondrocytes but that the active form, which degrades the extracellular matrix, is the MMP-1 that accumulates in the pericellular spaces around hypertrophic chondrocytes.

Alcian Blue↗

PubMed1990

Defective generalized extracellular matrix in the neoplasm bearing host: decreased inflammation, immunity and resistance.

Neoplasms have extensive qualitative and quantitative changes in their extracellular matrix. Lytic factors from neoplasms breakdown extracellular matrix of the areas adjacent to the neoplasms and fibroblasts in these areas produce increased extracellular matrix. Some of the extracellular matrix fractions are normally present in serum. Multiple fractions derived from extracellular matrix are present in the serum of tumor patients. Tumor patients often have decreased early cellular inflammation and immunity. These reactions depend on a normal extracellular matrix. A number of known facts about the tumor bearing host can be explained by the concept that the host's generalized extracellular matrix is altered by circulating fractions of extracellular matrix. These could be qualitative or quantitative defects as well as an abundance of depolymerized fractions. The beneficial effects of cytokines, streptococcal infections and pyridoxine deficiency on tumors can be explained by this concept.

Animals↗

PubMed1991

The remodeling of synaptic extracellular matrix and its dynamic relationship with nerve terminals at living frog neuromuscular junctions.

The question of whether the synaptic extracellular matrix undergoes remodeling and how this remodeling is related to nerve terminal plasticity was examined in living neuromuscular junctions of adult frogs. Sartorius muscles were double stained with a fluorescent nerve terminal dye 4-(4-diethylamino-styryl)-N-methylpyridinium iodide (4-Di-2-Asp) and rhodamine-tagged peanut agglutinin (PNA) which recognizes synaptic extracellular matrix. Both nerve terminals and synaptic extracellular matrix in 200 identified normal junctions were visualized in vivo two or three times over a period of 2.6-6 months. The majority of neuromuscular junctions (NMJs) showed remodeling of both nerve terminals and synaptic extracellular matrix. Only 2.5% showed no changes in either synaptic element. The most commonly seen remodeling involved correlated changes in both nerve terminals and synaptic extracellular matrix. In this large group, while some junctions (20%) showed overall proportionate changes in all branches, most junctions (68%) showed disproportionate extension and/or retraction of some but not all individual branches. Another group of NMJs (9.5%) showed mismatched changes in the nerve terminal and synaptic extracellular matrix. In this group, some NMJs showed a decrease in the nerve terminal length without a corresponding reduction in synaptic extracellular matrix length. In other junctions that displayed extension of branches, the PNA-stained matrix was longer than the distal tip of the nerve terminal. Morphometric analysis indicated an average increase of 15.6% in total nerve terminal length and 13.6% in total synaptic extracellular matrix length. Although almost all NMJs displayed remodeling in at least one branch, about 50% of the 2201 individual branches examined did not show changes. The average change was 8.9% growth in the length of individual nerve terminal branches and 8.3% growth in the length of individual branches of synaptic extracellular matrix. There was no significant difference in the morphometry between the repeatedly observed junctions and the previously unobserved control junctions. Furthermore, junctions in which the synaptic extracellular matrix was longer than the nerve terminal also were seen in control as well as in experimental muscles. Cases where the nerve terminals were longer than the synaptic extracellular matrix were never observed in newly arising junctional branches. The present study has shown extensive remodeling in not only the nerve terminal but also the synaptic extracellular matrix in adult living frog NMJs. Results suggest that nerve terminals retract before the synaptic extracellular matrix. A hypothesis that extension of synaptic extracellular matrix precedes nerve terminal growth during synaptic remodeling is proposed.

Animals↗

PubMed1988

Participance of fibronectin and various collagen types in the formation of fibrous extracellular matrix in cardiosclerosis.

Investigation of the extracellular matrix composition of the left heart ventricle was carried out on autopsy material of subjects, aged from 60 to 70 years, in a number of cases, including: (1) tissue without cardiosclerosis; (2) granulation tissue formed 2 weeks after infarction; (3) post-infarctial fibrous scars; (4) diffuse cardiosclerosis in consequence of stenotic coronary atherosclerosis. Cryostat sections treated with highly specific antibodies to fibronectin and types I, III, IV and V collagens were examined by the indirect immunofluorescence technique. Fibronectin and the mentioned collagenous proteins were detected in the extracellular matrix of granulation tissue. In contrast, fibronectin and collagen type IV were not revealed in post-infarctial fibrous scars. Collagen types III and V were diffusely distributed in fibrous tissue, whereas collagen type I was demonstrated to accumulate preferentially in the deeper regions of post-infarctial scars. Fibronectin and collagen types I, III, V, but never type IV, were also found in the connective tissue in diffuse cardiosclerosis. The significance of type V collagen in the extracellular matrix is discussed.

Aged↗

PubMed2002

Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions.

Remodeling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Thus, identifying factors that control the balance between matrix deposition and degradation during tissue remodeling is essential for understanding mechanisms that regulate a variety of normal and pathological processes. Using fibronectin-null cells, we found that fibronectin polymerization into the extracellular matrix is required for the deposition of collagen-I and thrombospondin-1 and that the maintenance of extracellular matrix fibronectin fibrils requires the continual polymerization of a fibronectin matrix. Further, integrin ligation alone is not sufficient to maintain extracellular matrix fibronectin in the absence of fibronectin deposition. Our data also demonstrate that the retention of thrombospondin-1 and collagen I into fibrillar structures within the extracellular matrix depends on an intact fibronectin matrix. An intact fibronectin matrix is also critical for maintaining the composition of cell-matrix adhesion sites; in the absence of fibronectin and fibronectin polymerization, neither alpha5beta1 integrin nor tensin localize to fibrillar cell-matrix adhesion sites. These data indicate that fibronectin polymerization is a critical regulator of extracellular matrix organization and stability. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix and cell-matrix adhesion sites provides cells with a means of precisely controlling cell-extracellular matrix signaling events that regulate many aspects of cell behavior including cell proliferation, migration, and differentiation.

Actins↗

PubMedDate not supplied

Dietary-induced atherosclerotic lesions have increased levels of acidic FGF mRNA and altered cytoskeletal and extracellular matrix mRNA expression.

Growth factor and extracellular matrix gene expression by vessel wall cells influence the development of arterial lesions. In this study, we compared the level of acidic and basic fibroblast growth factor mRNA expression in aortic vessels from normal swine and from swine with dietary-induced vascular lesions. There was a striking increase in the level of acidic fibroblast growth factor mRNA within the lesions while the level of basic fibroblast growth factor mRNA decreased. Swine fed an atherosclerotic diet supplemented with L-arginine developed atherosclerotic plaques that also contained increased levels of acidic fibroblast growth factor mRNA. We also examined the expression level of a number of extracellular matrix and cytoskeletal mRNAs to compare the biosynthetic state of normal arteries and atherosclerotic plaques. Compared with the normal artery, the level of alpha-smooth muscle actin mRNA decreased, and there was a concomitant increase in vimentin, fibronectin and thrombospondin mRNA levels. Surprisingly, alpha 1(I), alpha 2(I) and alpha 1(III) collagen mRNA levels were decreased in the atherosclerotic lesions when compared with the normal artery. These results indicate that vascular lesion formation in hypercholesterolemic swine is accompanied by alterations in growth factor, cytoskeletal and extracellular matrix gene expression.

Animals↗

PubMed1988

Molecular forms, binding functions, and developmental expression patterns of cytotactin and cytotactin-binding proteoglycan, an interactive pair of extracellular matrix molecules.

Cytotactin is an extracellular matrix protein that is found in a restricted distribution and is related to developmental patterning at a number of neural and non-neural sites. It has been shown to bind specifically to other extracellular matrix components including a chondroitin sulfate proteoglycan (cytotactin-binding [CTB] proteoglycan) and fibronectin. Cell binding experiments have revealed that cytotactin interacts with neurons and fibroblasts. When isolated from brain, both cytotactin and CTB proteoglycan contain the HNK-1 carbohydrate epitope. Here, specific antibodies prepared against highly purified cytotactin and CTB proteoglycan were used to correlate the biochemical alterations and modes of binding of these proteins with their differential tissue expression as a function of time and place during chicken embryo development. It was found that, during neural development, both the levels of expression of cytotactin and CTB proteoglycan and of the molecular forms of each molecule varied, following different time courses. In addition, a novel Mr 250,000 form of cytotactin was detected that contained chondroitin sulfate. The intermolecular binding of cytotactin and CTB proteoglycan and the binding of cytotactin to fibroblasts were characterized further and found to be inhibited by EDTA, consistent with a dependence on divalent cations. Unlike the molecules from neural tissue, cytotactin and CTB proteoglycan isolated from non-neural tissues such as fibroblasts lacked the HNK-1 epitope. Nevertheless, the intermolecular and cellular binding activities of cytotactin isolated from fibroblast culture medium were comparable to those of the molecule isolated from brain, suggesting that the HNK-1 epitope is not directly involved in binding. Binding experiments involving enzymatically altered molecules that lack chondroitin sulfate suggested that this glycosaminoglycan is also not directly involved in binding. Although they clearly formed a binding couple, the spatial distributions of cytotactin and CTB proteoglycan in the embryo were not always coincident. They were similar in tissue sections from the cerebellum, gizzard, and vascular smooth muscle. In contrast, CTB proteoglycan was present in cardiac muscle where no cytotactin is present, and it was seen in cartilage throughout development unlike cytotactin, which was present only in immature chondrocytes. Cell culture experiments were consistent with the previous conclusion that cytotactin was specifically synthesized by glia, whereas CTB proteoglycan was specifically synthesized by neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

The type II pneumocyte as a model of lung cell interaction with the extracellular matrix.

The influence of the extracellular matrix on differentiation and function of type II pneumocytes was investigated. Cells cultured on a plastic surface lost differentiated characteristics as they assumed a flattened, more attenuated phenotype. By the third day in primary culture, as the cells became less responsive to beta-adrenergic agonists, synthesis and secretion of phosphatidylcholine decreased and lamellar body content declined. Concomitantly, incorporation of [3H]thymidine into cellular DNA increased more than 10-fold. On a surface rich in fibronectin (FN), these transitions in form and function were accelerated. The effects of FN alone were similar to those of a FN-rich matrix deposited by type II cells cultured on plastic. These effects were inhibited when the FN surface was treated with anti-FN, or when the matrix was digested with proteases. In contrast, a laminin-rich matrix helped to maintain typical type II cell morphology and metabolism during culture. This effect was most evident in pneumocytes plated on matrigel (MG), a laminin-rich basement membrane-like gel formed from an extract of a mouse EHS sarcoma. MG inhibited cell flattening and the associated increase in thymidine incorporation; loss of differentiation on plastic was halted when the cells were overlaid with MG. Soluble components released from MG permitted cell flattening but, similar to complete MG, maintained low thymidine incorporation as time in culture was extended. These results show that both morphology and metabolism of cultured type II pneumocytes are influenced by the extracellular matrix.

Animals↗

PubMed1997

Extracellular matrix heparan sulfate modulates endothelial cell susceptibility to Staphylococcus aureus.

The ability of extracellular matrix heparan sulfate to alter the susceptibility of human endothelial cells to S. aureus was investigated. Endothelial cells grown on extracellular matrix synthesized by S. aureus-infected endothelial cells were more susceptible to subsequent staphylococcal infection than endothelial cells grown on the extracellular matrix synthesized by untreated endothelial cells. Endothelial cells were more susceptible to S. aureus infection when 1) grown on heparitinase-treated extracellular matrix that removed heparan sulfate chains, 2) grown on extracellular matrix produced by chlorate-treated endothelial cells that reduced sulfation in the matrix heparan sulfate proteoglycans, 3) grown on heparan sulfate purified from extracellular matrix elaborated by infected endothelial cells, and 4) endothelial cells were chlorate-treated and therefore expressed desulfated cellular heparan sulfate proteoglycans. Extracellular matrix produced by S. aureus-infected endothelial cells contained heparan sulfate proteoglycans with reduced sulfation. The altered extracellular matrix with reduced sulfated heparan sulfate proteoglycans signalled the uninfected endothelial cells to produce under sulfated cellular heparan sulfate proteoglycans that increased S. aureus adherence to the endothelial cells.

Bacterial Adhesion↗

PubMedDate not supplied

Extracellular matrix signaling through growth factor receptors during wound healing.

Recently, extracellular matrix components have been shown to contain domains that can interact with and activate receptors with intrinsic tyrosine kinase activity. These receptor tyrosine kinases are strong mediators of the cell responses of proliferation, migration, differentiation, and dedifferentiation. However, an interesting question is raised as to why cells would present growth factor receptor ligands in such a manner, as the majority of growth factors are small, soluble, or only transiently tethered ligands. With the exception of the discoidin domain receptors that bind collagen, the other described domains interact with a receptor that binds ubiquitous soluble peptide growth factors, the epidermal growth factor receptor. Unlike traditional growth factors, these individual "matrikine" domains within tenascin-C, laminin, collagen, and decorin possess relatively low binding affinity (high nanomolar or micromolar) and are often presented in multiple valency. The presentation of ligands within the extracellular matrix in this fashion might allow for unique biochemical and physiological outcomes. This new class of "matrikine" ligand may be critical for wound healing, as the majority of known extracellular matrix components possessing matrikines play a strong role, or are presented uniquely, during skin repair. Tenascin-C expression, for instance, is uniquely regulated spatially and has been proposed to present pro-migratory tracks during skin repair through its epidermal growth factor-like repeats. The epidermal growth factor-like repeats of laminin-5 act as cryptic ligands revealed upon matrix metalloproteinase-2 degradation of the surrounding extracellular matrix. The deletion of the discoidin domain receptors 1 and 2 for collagen have negative consequences on the role of fibroblasts and epithelial cells for matrix metalloproteinase production, migration, proliferation, and extracellular matrix turnover. Finally, decorin can bind to, inhibit, and down-regulate epidermal growth factor receptor levels and signaling, suggesting a tonic role of the epidermal growth factor binding domain of decorin in the resolution of wound healing. We provide a model framework for further studies into this emerging class of signals.

Animals↗

PubMed1997

The role of the extracellular matrix in arterial remodelling.

The extracellular matrix is now recognized as a biologically active and dynamic composition of structural, adhesive, and counteradhesive fibrous proteins embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans. The ability of resident cells to detect small differences in the specific combination, concentration and distribution of matrix components suggests that perturbation of the homeostatic matrix can lead to remodelling following angioplasty. Recent studies reviewed herein have focused on how alterations of the relative composition of matrix components ultimately leads to changes in cell growth, behaviour and differentiation, all of which can significantly contribute to remodelling of the vascular wall following injury. These cell-matrix interactions may provide novel therapeutic targets in the prevention of unfavourable remodelling that leads to restenosis.

Adaptation, Physiological↗

PubMed1997

Heparan sulfate-binding peptide promotes the deposition of proteoglycans in the extracellular matrix.

A synthetic peptide, which was shown to bind extracellular matrix heparan sulfate chains with a high degree of affinity and specificity [Colburn et al. (1996): Arch Biochem Biophys 325:129-138], has now been found to promote the transfer and the deposition of endothelial cell surface proteoglycans in the extracellular matrix. The peptide also induces preferential binding of extracellular matrix heparan sulfate proteoglycans, which have been added to the supernatant growth medium, and the requirement for its presence is stringent in that only a negligible amount of proteoglycans are bound to the cell layer in the absence of the peptide. In addition, antibodies directed against the peptide detect the accumulation of the peptide in the matrix compartment where the peptide is found associated with the proteoglycans transferred from the cell surface. The sequence of events induced by the peptide appears to be an extension of a naturally occurring process since proteoglycans with properties similar to those of the species ordinarily present in the extracellular matrix have been observed to transfer from the cell surface to the matrix during a pulse-chase experiment. We suggest that formation of the complex peptide-proteoglycan with consequent displacement of the proteoglycan from its anchorage on the cell initiates the process of transfer of the heparan sulfate-bound peptide from the cell surface to the extracellular matrix.

Animals↗