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Results for “Extracellular Matrix”

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PubMed1994

Neointima formation after acute vascular injury. Role of counteradhesive extracellular matrix proteins.

Restenosis currently limits the long-term beneficial effects of balloon coronary angioplasty. Two important cellular events in the development of clinically significant luminal narrowing after angioplasty are 1) increased production of extracellular matrix proteins and 2) acquisition of a motile phenotype by vascular smooth muscle cells. In this paper, smooth muscle cell responses that produce a fibrocellular neointima after acute vascular injury are reviewed. Particular emphasis is placed on specialized extracellular matrix proteins implicated in cell movement and tissue repair. Tenascin and thrombospondin are large, modular extracellular matrix glycoproteins; they possess both adhesive and counteradhesive domains and are expressed at high levels during smooth muscle cell migration and neointima formation after balloon injury to rat carotid artery. The ability of both tenascin and thrombospondin to down-regulate the assembly and activity of focal adhesions (points of cell-extracellular matrix adhesive interactions) may be important in the conversion of stationary, quiescent smooth muscle cells to cells that are able to move and divide within the strongly adhesive vessel wall. Moreover, tenascin is present in the extracellular matrix as a large 6-armed oligomer (a hexabrachion) that contains both cell-binding and matrix protein-binding domains in each of the hexabrachion arms. The large size and multidomain structure of tenascin and thrombospondin suggest that these proteins may be particularly well suited to form a nascent provisional matrix at sites of 1) neointima formation after acute vascular injury, 2) new growth and expansion within primary atherosclerotic plaques, and 3) intimal repair and luminal narrowing in restenosis after angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed1991

Neuronal interactions with the extracellular matrix.

The interactions of neurons with extracellular cues are important in directing the formation of precise neuronal networks during the development of the nervous system. This review will focus on recent progress towards the understanding of the molecular machinery involved in the interactions of neurons with the extracellular matrix.

Amino Acid Sequence↗

PubMed1984

Comparison of platelet interaction with subendothelium of human renal and umbilical arteries and the extracellular matrix produced by human venous endothelial cells.

Platelet interaction with subendothelium of human renal and umbilical arteries and with the extracellular matrix produced by cultured human venous endothelial cells was compared in flowing citrated blood by using an annular and a rectangular perfusion chamber. The renal arteries were post mortem specimens from adults showing, often pronounced, intimal fibrosis, whereas the umbilical arteries had well organized parallel arranged smooth muscle cells, without elastic membranes. The extracellular matrix obtained after removal of endothelial cells with Triton X-100 was homogenously attached to its substratum. Significantly more platelets adhered to the extracellular matrix than to the subendothelia. This discrepancy was most pronounced in reconstituted blood with plasma from a patient with homozygous severe von Willebrand's disease (subtype III). No differences in platelet adherence and platelet aggregate formation were noted between the subendothelia. Platelet aggregate formation was poor on all surfaces. These data indicate that the extracellular matrix produced by endothelial cells is at least as reactive for the interaction with platelets as subendothelium, probably partly synthesized by smooth muscle cells.

Arteries↗

PubMed1992

Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths.

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 x 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 x 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 x 10(3) Mr gelatinase, in particular, has a rate-limiting function in degradation of the maternal extracellular matrix by trophoblast cells.

Animals↗

PubMed1994

The extracellular matrix in pigmented skin lesions: an immunohistochemical study.

In recent years the interaction between tumour cells and the surrounding extracellular matrix in the process of tumour development, invasion and metastasis has been a focus of interest. We studied frozen sections of nine naevocellular naevi (junctional, compound and intradermal), 40 dysplastic naevi, six pagetoid in situ melanomas and 12 superficial spreading melanomas in order to determine the expression of: the basement membrane proteins collagen type IV and laminin, the interstitial collagen types I, III and VI, and fibronectin and tenascin. An indirect immunoperoxidase technique was used. In the various stages of melanocytic tumour progression we observed: 1 loss of type IV collagen and laminin within dermal melanocytic cell nests; 2 de novo expression of basement membrane type IV collagen and increased expression of the interstitial collagen types I, III and VI, as well as tenascin and fibronectin in the dermal stroma surrounding dysplastic naevus cells and melanoma cells; 3 presence of extracellular matrix components in close association with intra-epidermally located invading atypical melanocytes. These data demonstrate the complex alterations of the composition of the extracellular matrix from bland naevi through lesions with progressive atypia to invasive melanoma. The changes described result in a molecular environment which melanocytes with an altered adhesion molecule profile are able to invade.

Cell Adhesion Molecules, Neuronal↗

PubMed1990

Extracellular matrix and neuronal movement.

During brain development, both neuronal migration and axon guidance are influenced by extracellular matrix molecules present in the environment of the migrating neuronal cell bodies and nerve fibers. Glial laminin is an extracellular matrix protein which these early brain cells preferentially attach to. Extracellular glycosaminoglycans are suggested to function in restricting neuronal cell bodies and axons from certain brain areas. Since laminin is deposited along the radial glial fibers and along the developing nerve pathways in punctate form, the punctate assemblies may be one of the key factors in routing the developing neurons in vivo. This review discusses the role of laminin in neuronal movement given the present concept of the extracellular matrix molecules and their proposed interactions.

Animals↗

PubMed2001

Defects in extracellular matrix structural proteins in the osteochondrodysplasias.

Mutations in the genes that encode structural proteins of the extracellular matrix affect one or more steps in the diverse set of coordinated events necessary for ordered skeletal development. Depending on the role of the gene product and the severity of the defect, disruption of endochondral ossification and linear growth, the structural integrity and stability of articular cartilage, and/or mineralization can occur. Several themes have emerged from the molecular dissection of these disorders; most of the osteochondrodysplasias that result from defects in structural proteins are inherited in an autosomal dominant fashion; a spectrum of related clinical phenotypes can be produced by distinct mutations in the same gene; haploinsufficiency for the gene product usually produces a milder clinical phenotype than do mutations resulting in synthesis of structurally abnormal proteins. For structural defects, a dominant-negative effect resulting from presence of the abnormal protein in the matrix appears to be the primary determinant of phenotype. Secondary effects on extracellular matrix protein structure can result from defects in post-translational maturation, including hydroxylation, sulfation and proteolytic cleavage, and produce distinct osteochondrodysplasias. Overall, the inherited disorders of skeletogenesis have revealed the exquisite sensitivity of the architecture of the extracellular matrix to the quantity and quality of matrix molecules.

Animals↗

PubMed1994

Developmental expression in the rat cerebellum of SC1, a putative brain extracellular matrix glycoprotein related to SPARC.

In the nervous system, extracellular matrix (ECM) molecules have been shown to have effects on cell migration, process outgrowth and the survival of neurons. Recently we have described the molecular cloning of SC1, a putative brain extracellular matrix glycoprotein, showing partial similarity to the ECM glycoprotein SPARC/osteonectin. We have now examined the expression of SC1 during the development of the rat cerebellum at both the protein and mRNA levels. Our results indicate that SC1 is both temporally and spatially regulated during this process. Bergmann glial cells express SC1 mRNA and the resultant protein is deposited along the length of their radial fibres during the process of granule cell migration in the developing cerebellum. SC1 mRNA and protein is also found in the adult cerebellum, concentrated in the Bergmann glial cells and their radial processes, indicating that this putative ECM molecule continues to play roles in the central nervous system after migration and proliferative events have ceased.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed1992

Effect of spaceflight on the extracellular matrix of skeletal muscle after a crush injury.

The organization and composition of the extracellular matrix were studied in the crush-injured gastrocnemius muscle of rats subjected to 0 G. After 14 days of flight on COSMOS 2044, the gastrocnemius muscle was removed and evaluated by histochemical and immunohistochemical techniques from the five injured flight rodents and various Earth-based treatment groups. In general, the repair process was similar in all injured muscle samples with regard to the organization of the extracellular matrix and myofibers. Small and large myofibers were present within an expanded extracellular matrix, indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of nonmuscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well organized and contained more macrophages and blood vessels in the repair region, indicative of a delayed repair process, but did not demonstrate any chronic inflammation. Myofiber repair did vary in muscles from the different groups, being slowest in the flight animals and most complete in the tail-suspended ones.

Animals↗

PubMed1983

Cell attachment, growth characteristics and surface morphology of human upper-respiratory tract epithelium cultured on extracellular matrix.

The advantageous utilization of nasal polypoid tissue as a source for human epithelial cells and the dramatic effect of extracellular matrix on growth and differentiation of these cells were demonstrated. Plating on extracellular matrix induced rapid, firm, cell attachment and flattening of the explants, promoted cell outgrowth as well as long-term survival of epithelial cells in primary cultures. Prominent ciliary activity was observed on the cells of the explant and on the cells in the outgrowth. These cells could be maintained on the extracellular matrix coated dishes for prolonged periods even after removal of the explant, with the cells in the outgrowth covering the region occupied by the removed explant. Prominent ciliary activity, which is considered one of the main criteria for cell viability and differentiation, continued also in the absence of the explant. The present system for cultivation of human upper respiratory tract epithelial cells on extracellular matrix might prove of value in analysing effects of chemotherapeutic agents that influence normal differentiation as well as the effects of viral and chemical carcinogens on these cells in human respiratory disease.

Adult↗

PubMed2002

The dynamic interaction of the extracellular matrix in cardiac remodeling.

The dynamic interaction of the extracellular matrix (ECM) with the various cellular components of the heart is a fundamental process in cardiac remodeling. These cellular components include myocytes, and connective tissue cells adapt to the signals from the extracellular environment. Critical to this dynamic interaction are several classes of transmembrane receptors that provide both inside-out and outside-in signaling.

Collagen↗

PubMed1994

Immunohistochemical characterization of extracellular matrix components of granulosa cell tumor of ovary.

In order to clarify the characteristics of granulosa cell tumors of the ovary, extracellular matrix components were investigated by immunohistochemical techniques. Twenty-three granulosa cell tumors (GCT; eight juvenile and 15 adult type) were studied in comparison with non-neoplastic granulosa cells of human ovaries. In all 23 cases of GCT, chondroitin 6-sulfate proteoglycan revealed with antibody 3B3 was characteristically observed in the extracellular matrix in the solid nest, as well as in microfollicles. In the juvenile cases, the extracellular matrix also contained large proteoglycan (PG) revealed with antibody 2B1. Macrofollicles as well as microfollicles contained PG chondroitin 6-sulfate side chains with a significant amount of chondroitin 4-sulfate. By biochemical analysis using high pressure liquid chromatography, it was also found that disaccharide composition of glycosaminoglycan fractions extracted from granulosa cell tumor tissues consisted mainly of 2-acetamide-2-deoxyl-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (delta Di-6S). The characteristic feature of granulosa cell tumors is the accumulation of chondroitin sulfate PG, especially chondroitin 6-sulfate PG, which may be synthesized by the tumor cells themselves. Immunohistochemical characterization of the extracellular matrix components (collagen, laminin, heparan sulfate PG, chondroitin 4-sulfate PG) was also studied in relation to chondroitin 6-sulfate PG localization.

Adolescent↗

PubMed1990

Human endometrial cells grown on an extracellular matrix form simple columnar epithelia and glands.

Normal human endometrial cells were grown on an extracellular matrix containing type IV collagen, laminin, heparan sulfate proteoglycan, and entactin (Matrigel). On the extracellular matrix, dispersed endometrial cells remained rounded, and aggregated to form mounds of cells, which continued to grow in this arrangement. At 10 d, light microscopy demonstrated that these mounds were comprised of an eosinophilic substance, containing individual fusiform stromal cells. About 50% of the mounds were covered with a single layer of polarized cuboidal to columnar cells with basal nuclei, whereas 60% contained columnar cells forming glandular structures with open lumina. These polarized cuboidal and columnar cells were epithelial, based on their positive staining for cytokeratins and the possession of microvilli, tonofilaments, abundant glycogen, ribosomes, and primitive junctional complexes. Kreyberg's stain showed the presence of mucin within the lumina of the glands, indicating that they were functional. Thus, human endometrial cells grown on an extracellular matrix form a simple cuboidal to columnar epithelium, a stromal component, and glandular structures, thereby mimicking the in vivo morphology of the endometrium.

Cell Division↗

PubMed1992

Activation of extracellular matrix metalloproteases by proteases and organomercurials.

Extracellular matrix metalloproteases are synthesized as proenzymes and are activated by certain physiological agents after secretion into the extracellular space. The identity of these agents and the stimulus that elicits their response in vivo is only recently becoming clear, but a variety of agents or stimuli are capable of activating these metalloproteases in vitro also. Of these, the most well studied and characterized are trypsin, plasmin and the organomercurials. These agents appear to have in common an ability to disrupt the structure of the stable latent enzyme in such a way as to allow the generation of a proteolytic active site. In the case of organomercurial activation, intramolecular proteolytic cleavage of the amino-terminus of the enzyme occurs subsequent to generation of activity. A similar intramolecular process is seen with trypsin and plasmin activation except that it is initiated by a single trypsin or plasmin catalyzed cleavage in the amino-terminus prior to the autocatalytic cleavages. A possible explanation for organomercurial activation is that the mercurial disrupts a cysteinyl residue coordination bond with the active site zinc that prevents interaction with substrate. Disruption of this complex would allow productive enzyme-substrate interaction via the newly available coordination site. In addition, activated stromelysin is capable of increasing the specific activity of active interstitial collagenase by approximately ten-fold through what appears to be proteolytic removal of a small peptide.

Amino Acid Sequence↗

PubMedDate not supplied

Lung injury and degradation of extracellular matrix components by Aspergillus fumigatus serine proteinase.

Aspergillus fumigatus produces a variety of extracellular proteinases that are believed to be virulence factors towards Aspergillus-related lung disease. Among Aspergillus proteinases, the serine proteinase is thought to play a major virulent role because of its widespread production. Nevertheless, evidence of direct pulmonary injury caused by the A. fumigatus serine proteinase is still lacking. The purpose of our work was: (1) to provide evidence for a pivotal role of A. fumigatus serine proteinase in producing lung injury in an animal model, and (2) to investigate the broadness of the substrate specificity of the proteinase towards extracellular matrix components. To achieve this aim, the proteinase from an A. fumigatus strain isolated from human airways was purified by a four-step procedure, including cation exchange and hydrophobic interaction. High-performance capillary electrophoresis, SDS-PAGE, determination of K(m) towards synthetic substrates, and inhibitory studies were used to further characterize the A. fumigatus serine proteinase. With reference to extracellular matrix components, the A. fumigatus serine proteinase was shown to degrade human lung elastin at a higher rate than an equimolar amount of human neutrophil elastase. Human lung collagen, type I and type III collagens, as well as fibronectin, were quickly digested by the A. fumigatus serine proteinase. Finally, mice intratracheally injected with the proteinase showed a significant degree of lower respiratory tract destruction. We conclude that the A. fumigatus serine proteinase is capable per se of hydrolyzing the major structural barriers of the lung.

Animals↗

PubMed1995

Extracellular matrix components in intestinal development.

Intestinal morphogenesis and differentiation are dependent on heterotypic cell interactions between embryonic epithelial cells (endoderm) and stromal cells (mesenchyme). Extracellular matrix molecules represent attractive candidates for regulators of these interactions. The structural and functional diversity of the extracellular matrix as intestinal development proceeds is demonstrated by 1) spatio-temporal specific expression of the classically described constituents, 2) the finding of laminin and collagen IV variants, 3) changes in the ratio of individual constituent chains, and 4) a stage-specific regulation of basement membrane molecule production, in particular by glucocorticoids. The orientation/assembly of these extracellular matrix molecules could direct precise cellular functions through interactions via integrin molecules. The involvement of extracellular matrix, and in particular basement membrane molecules in heterotypic cell interactions leading to epithelial cell differentiation, has been highlighted by the use of experimental models such as cocultures, hybrid intestines and antisense approaches. These models allowed us to conclude that a correct elaboration and assembly of the basement membrane, following close contacts between epithelial and fibroblastic cells, is necessary for the expression of differentiation markers such as digestive enzymes.

Animals↗

PubMed1994

Specific effects of glycosaminoglycans in an analog of extracellular matrix that delays wound contraction and induces regeneration.

Previous studies have shown that a simple analog of extracellular matrix delays wound contraction and, if seeded with keratinocytes, inhibits scar synthesis by inducing partial regeneration of the dermis and the epidermis in full-thickness skin wounds in the guinea pig. The active extracellular matrix analog was selected from a large number of copolymers of type I collagen and chondroitin-6-sulfate differing in average pore diameter and degradation rate. However, these previous studies did not provide information on the potential role of the glycosaminoglycan component of this collagen-glycosaminoglycan matrix. The present study focuses on the effect of substitution of chondroitin-6-sulfate by other glycosaminoglycans or with the corresponding proteoglycans. The three substituents of chondroitin-6-sulfate studied were dermatan sulfate, decorin (a proteoglycan-containing dermatan sulfate chain), and aggrecan (a proteoglycan in which 90% of the glycosaminoglycan component was chondroitin-6-sulfate). Each test matrix was grafted on full-thickness skin wounds in the guinea pig, and the wound contraction kinetics were followed. Previous studies have strongly suggested that delay in onset of contraction is necessary for regeneration. Substitution of chondroitin-6-sulfate by either dermatan sulfate or decorin increased the delay in wound contraction by the greatest increment. However, the difference between substitution either by the dermatan sulfate chains or by the corresponding proteoglycan was not significant. Substitution of chondroitin-6-sulfate by aggrecan did not affect the activity of the extracellular matrix analog. These results suggest that the glycosaminoglycan component of the proteoglycan, rather than the protein core, is responsible for the increment of activity. It is speculated that the morphogenetic activity of the extracellular matrix analog resides in its putative ability to neutralize transforming growth factor-beta, leading thereby to downregulation of the inflammatory response in the wound bed.

Journal Article↗

PubMed2004

Extracellular matrix glycoproteins and diffusion barriers in human astrocytic tumours.

The extracellular matrix (ECM) and changes in the size and geometry of the extracellular space (ECS) in tumour tissue are thought to be of critical importance in influencing the migratory abilities of tumour cells as well as the delivery of therapeutic agents into the tumour. In 21 astrocytic neoplasms, the ECM composition was investigated in situ by the immunohistochemical detection of ECM glycoproteins (tenascin, laminin, vitronectin, fibronectin, collagen types I-VI). To explain the changes in ECS size and to detect barriers to diffusion in the tumour tissue, the ECM composition, the cellularity, the density of glial fibrillary acidic protein (GFAP)-positive tumour cell processes and the proliferative activity of the tumours were compared with the size and geometry of the ECS. The ECS volume fraction and the complex of hindrances to diffusion in the ECS (i.e. the tortuosity) were revealed by the real-time iontophoretic tetramethylammonium method. Increased proliferative activity of the tumours correlated with increased ECS volume fraction and tortuosity. The tortuosity of the tumour tissue was not significantly influenced by tumour cell density. Higher tortuosity was found in low-grade astrocytomas associated with the presence of a dense net of GFAP-positive fibrillary processes of the tumour cells. The increase in tortuosity in high-grade tumours correlated with an increased accumulation of ECM molecules, particularly of tenascin. We conclude that the increased malignancy of astrocytic tumours correlates with increases in both ECS volume and ECM deposition.

Aged↗