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At least 667 records · Page 37Linked to original sources

PubMed1992

Tenascin: a potential modulator of cell-extracellular matrix interactions during vertebrate embryogenesis.

Tenascin is a large oligomeric extracellular matrix (ECM) glycoprotein whose expression is highly restricted during vertebrate development. It has a characteristic hexameric quaternary structure with six arms linked to a central globular domain. Each arm contains a single polypeptide with the central globular domain formed by the covalent association of the N-terminal ends of the six polypeptides. Tenascin first appears during development, associated with the neural crest cell migration pathways of mammalian, avian and amphibian embryos. During later development, it is observed at sites of cartilage, bone and tendon formation. Tenascin expression also occurs in defined areas in the developing nervous system and in condensing mesenchyme, in response to epithelio-mesenchymal interactions. The function of tenascin in these different morphogenetic processes is not yet clearly understood. Tenascin can promote neurite outgrowth in vitro and can inhibit cell interactions with fibronectin. Results based on antibody mapping and molecular cloning indicate that these properties involve two distinct cell binding sites. Together with its highly regulated expression in the embryo, these properties suggest that tenascin plays a key role in the control of cell migration and differentiation during development.

Animals↗

PubMed1996

[Cell adhesion molecules and extracellular matrix components as target structures of autoimmunity].

A number of cell-cell and cell-matrix adhesion molecules as well as several extracellular matrix components represent target structures of antibody-mediated autoimmunity which recently have been extensively characterized at the molecular biological level. Pathogenic autoantibodies against these molecules have been found to be causally related to disturbances of cell and tissue adhesion that become apparent as various (muco-)cutaneous blistering diseases. In desmosomes, desmosomal cadherins (desmogleins and desmocollins) mediate epidermal intercellular adhesion. Among these, desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, being characterized by intraepidermal blistering. The pathogenic relevance of autoantibodies against desmocollins (IgA pemphigus and other pemphigus types) and desmoplakins (paraneoplastic pemphigus) still remains unclear. Hemidesmosomes contain the plaque protein BPAG1 and the partly collagen-like transmembrane protein BPAG2, representing the autoantigens of bullous pemphigoid and pemphigoid gestations which show subepidermal blistering. A certain subtype of cicatricial (benign mucous membrane) pemphigoid is characterized by autoantibodies against laminin 5 present in the subhemidesmosomal anchoring filaments. Both epidermolysis bullosa acquisita and bullous SLE exhibit autoantibodies against collagen type VII which constitutes the anchoring fibrils. Besides, autoantibodies against a particular collagen type IV chain of the glomerular basement membrane are responsible for the manifestation of Goodpasture's syndrome. These recent molecular biological findings might be the basis for the development of novel therapeutic strategies.

Animals↗

PubMed1997

Abnormalities of the extracellular matrix in keratoconus corneas.

PURPOSE: To study alterations of the extracellular matrix (ECM) and basement membrane (BM) components in human keratoconus corneas. METHODS: Fifteen normal and 13 keratoconus corneas were characterized by immunofluorescence with antibodies to 23 ECM and BM components. RESULTS: Keratoconus staining patterns for posterior nonscarred regions and Descemet's membrane were normal. We focused on three areas of keratoconus corneas: (a) nonscarred anterior corneal regions, (b) scarred anterior and posterior corneal regions, and (c) gaps in Bowman's layer. In each of these areas, consistent ECM and BM changes could be found. Nonscarred regions showed decreased staining of the epithelial BM for entactin/nidogen, fibronectin, alpha 3-alpha 5 chains of type IV collagen, and chains of laminin-1. In contrast, scarred regions had greater than normal staining of the epithelial BM for these same components and also for laminin-5, perlecan, and type VII collagen. In the Bowman's layer gaps/breaks, focal fibrotic deposits containing type VIII collagen, fibrillin-1, tenascin-C, alpha 1-alpha 2 type IV collagen, and normal stromal ECM and epithelial BM components were seen. Fibrotic regions were largely restricted to areas where, because of the lack of Bowman's layer, the epithelium was in contact with the stroma. CONCLUSIONS: In a single keratoconus cornea, abnormalities in the ECM/BM patterns were not uniform. This may reflect locally increased protease activity (where few if any BM components are found) and ongoing wound healing (where more BM or ECM components or both are found).

Adult↗

PubMed1988

Detection of extracellular matrix molecules synthesized in vitro by monkey and human retinal pigment epithelium: influence of donor age and multiple passages.

The retinal pigment epithelium of various species, including man, can synthesize extracellular matrix components in vitro. We studied extracellular matrix molecule production by human, rhesus and cynomolgus monkey pigment epithelium in vitro, using a panel of specific antibodies to collagen types I-V, fibronectin, laminin, the basement membrane heparan sulfate proteoglycan, human alpha elastin, glial fibrillary acidic protein (GFAP), and Factor VIII in a modified indirect immunofluorescence reaction. Results were similar between human and both monkey species in early passage cultures with respect to the positive detection of collagen types I, III, IV, V laminin, basement membrane proteoglycan, and fibronectin. The fluorescence was strongest in the center of confluent monolayers and was absent in border or isolated cells. Collagen type II, elastin, GFAP, or Factor VIII were not detected. Based on these findings, human and monkey pigment epithelium in vitro should be useful for the study of the synthesis, deposition and supramolecular interactions of a variety of extracellular matrix molecules.

Aging↗

PubMed1993

Regulation of extracellular matrix proteins and integrin cell substratum adhesion receptors on epithelium during cutaneous human wound healing in vivo.

Although changes in extracellular matrix proteins during wound healing have been well documented, little is known about the regulation of corresponding extracellular matrix adhesion receptors (integrins). To study this process in a human in vivo model, full thickness human skin grafts were transplanted onto severe combined immunodeficient mice and deep excisional wounds involving both the epidermal and dermal layers were then made. The changes in the expression of cell matrix proteins and epithelial integrins over time were analyzed with specific antibodies using immunohistochemistry. Wounding was associated with alterations in extracellular matrix proteins, namely, loss of laminin and type IV collagen in the region of the wound and expression of tenascin and fibronectin. Changes were also noted in the integrins on the migrating keratinocytes. There was marked up-regulation of the alpha v subunit and de novo expression of the fibronectin receptor (alpha 5 beta 1) during the stage of active migration (days 1 to 3 after wounding). In the later stages of wound healing, after epithelial integrity had been established, redistribution of the alpha 2, alpha 3, alpha 6, and beta 4 collagen/laminin-binding integrin subunits to suprabasal epidermal layers was noted. Thus, during cutaneous wound healing, keratinocytes up-regulate fibronectin/fibrinogen-binding integrins and redistribute collagen/laminin-binding integrins. This study demonstrates that the human skin/severe combined immunodeficient chimera provides a useful model to study events during human wound repair.

Animals↗

PubMed1996

Cell-extracellular matrix interactions in the ductus arteriosus and perinatal pulmonary circulation.

Our studies and those of others have shown that changes in the extracellular matrix have profound effects on vascular remodeling. In the ductus, increased production of endothelial hyaluronan and smooth muscle cell chondroitin sulfate and fibronectin and impaired elastin fiber assembly are features critical to smooth muscle cell migration into the subendothelium and intimal cushion formation. There is a developmentally orchestrated process that involves post-transcriptional mechanisms of gene regulation. Closure of the ductus arteriosus is associated with further changes in matrix expression and programmed cell death. The changes in the extracellular matrix that induce neointimal formation are also observed in pathological conditions in pulmonary and coronary arteries. Plasticity of the pulmonary circulation in the perinatal period also involves matrix regulation, and processes that prevent the normal decrease in pulmonary vascular resistance will result in impaired matrix regulation, and in the development of structural changes in the pulmonary arteries, including abnormal smooth muscle cell differentiation, hypertrophy and proliferation, which sustain the elevation in pulmonary artery pressure.

Animals↗

PubMed1989

Effects of interleukin-1 on fibroblast extracellular matrix, using a 3-dimensional culture system.

This study describes the alterations induced by Interleukin-1 alpha and -beta (IL-1 alpha and IL-1 beta) on fibroblast-synthesized extracellular matrix. Fibroblasts were grown between pieces of dentin or in collagen-coated Terasaki wells for 3 or 6-9 weeks to create 3-dimensional cell-containing matrices constituted primarily of proteoglycans and collagens, respectively. Following incubation with IL-1 alpha or IL-1 beta (10(-9) M) at 37 degrees C for 24 or 72 hr, samples were prepared for light and electron microscopy. Both IL-1 alpha and IL-1 beta induced collapse of the extracellular matrix by 72 hr, as manifested by a decrease of the cross-sectional area and an increased density of the matrices. Three-week matrices were reduced 26% and 45% by using IL-1 alpha and IL-1 beta, respectively. Comparable values obtained by using 6-week matrices were 14% and 30%. Cells within the matrix, normally stellate in shape with numerous extended processes, attained a more rounded or spindle shape with few and reduced processes and showed apparent alterations at cell matrix attachment sites and rearrangement of the cytoskeleton. Elongated cells at the top of the matrix appeared more compressed. The alterations were more pronounced in cultures incubated with IL-beta than with IL-1 alpha. Immunocytochemistry of extracellular matrix components revealed a decrease in staining intensity of chondroitin and dermatan sulfate in the 3-week matrix following IL-1 beta incubation. There was also a decrease in collagen type 1 staining of 9-week matrices treated with IL-1 alpha or IL-1 beta. These studies show that IL-1 has an effect on fibroblast-synthesized extracellular matrix and indicate that the effects of IL-1 alpha and IL-1 beta may differ. The resulting collapse of the matrix appears at least in part to be due to changes in proteoglycans and collagens.

Actin Cytoskeleton↗

PubMed2000

Biglycan-like extracellular matrix genes of agnathans and teleosts.

Biglycan and decorin are two members of a family of small extracellular matrix proteoglycans characterized by the presence of 10 leucine-rich repeats and one or two attachment sites for glucosaminoglycans. Both have thus far been described only from tetrapod species, mainly mammals. Because the extracellular matrix has played an important part in the evolution of Metazoa, the phylogeny of its components is of considerable interest. In this study, biglycan-like (BGL) cDNA sequences have been obtained from two teleost (Oreochromis cichlid and zebrafish) and two lamprey species. The analysis of the sequences suggests that, like tetrapods, the lampreys possess two types of proteoglycans, both of which are biglycan-like; decorin-like proteoglycans could not be identified in these species. The genes specifying these two types apparently arose by duplication in the lamprey lineage after its divergence from gnathostomes. The two teleost species possess a BGL proteoglycan and a bona fide decorin. The BGL proteoglycan is highly divergent from the tetrapod biglycan and related to the BGL proteoglycans of the lamprey. Hence, although the duplication generating the ancestors of biglycan and decorin genes occurred after the divergence of agnathans but before the emergence of teleosts, only decorin acquired its characteristic properties in the bony fishes. The BGL gene presumably turned into a typical biglycan only in the tetrapod lineages. The presumed acquisitions of new functions appear to have been accompanied by changes in the evolutionary rate.

Amino Acid Sequence↗

PubMed1992

The extracellular matrix in the failing human heart.

The composition of the extracellular matrix was investigated in eight human hearts explanted at the time of transplantation surgery because of endstage cardiomyopathy. All patients showed clinical signs of heart failure. The tissue was investigated by electron microscopy and immunofluorescence microscopy using monoclonal antibodies against collagen I, III, VI, and IV, fibronectin, laminin, and vimentin. All matrix proteins occurred in increased amounts in the extracellular space separating the myocardial cells by septa of enlarged thickness. Laminin and collagen IV surrounded myocardial and endothelial cells as layers of increased thickness. Vimentin localization was normal in individual cells, but occurred more often and corresponded to the numerous fibroblasts as observed by electron microscopy. It is concluded that an excessive deposition of extracellular matrix material in addition to myocyte degeneration (as reported previously (9)) are the structural correlates of cardiac failure.

Cardiomyopathy, Dilated↗

PubMed2003

Human renal fibroblasts derived from normal and fibrotic kidneys show differences in increase of extracellular matrix synthesis and cell proliferation upon angiotensin II exposure.

Angiotensin II (Ang II) as a vasoactive hormone may be involved in progressive renal interstitial fibrosis. We investigated the influence of Ang II on cell proliferation and synthesis of extracellular matrix (collagen I, III and fibronectin) in human renal fibroblasts derived from normal (TK 173 cell line) and fibrotic (TK 188 cell line) kidneys which possess both Ang II type l and type 2 (AT1 and AT2) receptors. Incubation of the cells with Ang II increased the cell proliferation and the synthesis of extracellular matrix significantly in both cell lines. However, proliferation and extracellular matrix synthesis showed a greater increase in the cells derived from the fibrotic kidney. The Ang II mediated effect on cell proliferation and extracellular matrix synthesis was diminished in the presence of the AT1 receptor blocker losartan in both cell lines. No inhibition was observed using the AT2 receptor blocker PD123319. Ang II induced cell proliferation could be completely inhibited by incubation with human TGF-beta1 antibody. Incubation with Ang II did not affect TGF beta 1 production but in untreated cells TGF-beta 1 content was higher in the cells derived from the fibrotic kidney. This might be the reason for the more sensitive reaction on exposure to Ang II.

Angiotensin II↗

PubMed2000

Extracellular matrix and nuclear localization of beta ig-h3 in human bladder smooth muscle and fibroblast cells.

The extracellular matrix (ECM) plays an essential role in bladder structure and function. In this study, expression of beta ig-h3, a recently identified extracellular matrix protein, was investigated in human bladder tissue, and human bladder smooth-muscle (SMC) and fibroblast cells in vitro. SMCs secreted greater than three times the level of this protein compared with fibroblasts. The relative levels of beta ig-h3 mRNA in the two cell types reflected the protein expression. Immunohistochemical analysis demonstrated protein deposition in the ECM as well as cytoplasmic localization and, unexpectedly, nuclei. Anti-beta ig-h3 antibodies also stained the matrix surrounding the detrusor SMCs and nuclei of bladder fibroblasts, SMCs, and urothelium in intact bladder tissue. Western blot analyses of medium and matrix fractions obtained from cells in vitro revealed protein of approximately 70-74 kDa, whereas nuclear extracts contained a 65-kDa reactive protein band. We propose that although this protein is a structural component of bladder ECM, its nuclear localization suggests that it has other regulatory and/or structural functions.

Amino Acid Sequence↗

PubMed1994

Tyrosine-rich acidic matrix protein (TRAMP) is a tyrosine-sulphated and widely distributed protein of the extracellular matrix.

Tyrosine-rich acidic matrix protein (TRAMP; 22 kDa extracellular matrix protein; dermatopontin) is a protein that co-purifies with lysyl oxidase and with dermatan sulphate proteoglycans, with possible functions in cell-matrix interactions and matrix assembly. Using a rabbit polyclonal antiserum raised against porcine TRAMP, which cross-reacts with both the human and murine forms of the protein, we show by immunoblotting that TRAMP has a widespread tissue distribution, including skin, skeletal muscle, heart, lung, kidney, cartilage and bone. In cultures of human skin fibroblasts, TRAMP incorporates both [35S]sulphate and [3H]tyrosine and is secreted into the medium, as shown by immunoprecipitation. Amino acid analysis of immunoprecipitated TRAMP demonstrates that many of the tyrosine residues in TRAMP are sulphated.

Animals↗

PubMed2001

Extracellular matrix proteins in cardiac fibroblasts derived from rat hearts with chronic pressure overload: effects of beta-receptor blockade.

Left ventricular hypertrophy (LVH) is accompanied by progressive accumulations of extracellular matrix proteins. They are produced predominantly by cardiac fibroblasts that surround the cardiac myocytes. The aim of this study was to emphasize the role of a combined approach using both in vivo and in vitro studies to elucidate the effects of carvedilol on cardiac remodeling. We therefore used an established model of supravalvular aortic banding and cardiac fibroblasts. LVH was induced by banding of the ascending aorta. Male Wistar rats were allocated to four groups: sham-operated, sham+carvedilol, aortic stenosis (AS), and AS+carvedilol. Treatment time was four weeks. Fibroblasts were isolated from the entire left ventricle of sham and AS rats. Carvedilol/metoprolol/prazosin were added (0.1, 1.0 and 10 microM; 24 h). In addition, interferon- gamma was applied for 24 h (10, 100 and 1000 IU). AS rats revealed increased LV weights (+27%) and cardiomyocyte widths as compared to sham-operated rats (1.6-fold, P<0.01). Carvedilol reduced LVH by 20%. This finding was accompanied by a decrease of laminin, fibronectin, collagen I and III in vivo. Collagen I/III and fibronectin were increased in fibroblasts of AS v sham rats (P<0.0001, each). Carvedilol reduced collagen I, III and fibronectin by 40/60/35% (0.1 microM; P<0.001) irrespective of LVH. Carvedilol had no effects on collagen IV and laminin. Carvedilol dose-dependently reduced the proliferation rate by 20% at 0.1 microM(P<0.0001). Metoprolol and prazosin had no effect on the expression of extracellular matrix proteins and on the proliferation of the cells of either origin. Interferon- gamma blunted the proliferation rate of cultured fibroblasts and lead to a significant decrease in extracellular matrix deposits. These results indicate that the effects of carvedilol may be due to the antiproliferative or antioxidative properties of this unselective beta-adrenergic receptor antagonist. These changes of the extracellular matrix represent a new mechanism of carvedilol that may contribute to the observed beneficial effects in congestive heart failure.

Adrenergic beta-1 Receptor Antagonists↗

PubMed2004

Human ovarian tissue cultures: extracellular matrix composition, coating density and tissue dimensions.

Human ovarian tissue can be successfully cryopreserved for fertility preservation. Optimal use of this approach requires the development of reliable restoration methods, including in-vitro culture of follicles. A culture system has been established, but improvement of the basic handling and techniques is necessary. Ovarian biopsies were collected from 33 women, cut into small pieces and cultured for 7-14 days on an extracellular matrix. Three separate studies investigated tissue dimensions (slices and cubes), coating density of extracellular matrix (diluted, thin and thick), and different extracellular matrix compositions (regular Matrigel, growth factor reduced Matrigel and laminin). Initial recruitment of primordial follicles and reduction in follicle viability was observed in all cultures compared with uncultured tissue. After 7 days of culture, more viable follicles were present in the cubed tissue, which also showed significant activation of growth, observed in tissue slices only after 14 days of culture. A diluted coating of Matrigel supported a greater proportion of viable follicles in 7-day cultures, whereas composition of the extracellular matrix had no effect. Human ovarian follicles can grow and develop in vitro within cortical tissue, and may benefit from culture as cubes on diluted Matrigel. This technique may provide a solution to the successful recovery and growth of follicles from frozen human ovarian tissue even though it will take time and much more optimization before it can be used in clinical practice.

Adult↗

PubMed1987

Interaction of tumor cells with the extracellular matrix.

Cancer cell invasion of the normal tissue surrounding a growing neoplasm and the subsequent spread (metastasis) of malignant cells throughout the body is the major cause of the morbidity and mortality associated with malignant disease. At the primary tumor site, local invasion may be minimal as in the case of human malignant melanomas. Yet this tumor has the propensity to disseminate widely. On the other extreme, squamous carcinomas of the head and neck may produce a tremendous amount of host tissue destruction at the primary site. These tumors tend to be highly-invasive locally but disseminate more slowly than other forms of cancer such as malignant melanomas. In a like fashion, malignant melanomas tend to be surrounded by only minimal stroma while other tumor types produce a large amount of extracellular matrix themselves or induce matrix production by normal host tissue cells. In spite of the many tumor type specific differences which exist, recent studies in the field of cancer metastasis have identified features that are common to all invasive and metastatic tumors. This includes adhesion of invading tumor cells to host extracellular matrix structures, degradation of host tissue and active tumor cell movement through the partially degraded tissue. The critical events that occur during the invassion and metastatic processes are mediated through interactions between invading tumor cells and the extracellular matrix of the host. The expression of cell surface receptors for extracellular matrix molecules and the synthesis/expression of extracellular matrix molecules, themselves, on the surface of malignant tumor cells are thought to underline the events that are critical to the invasion and metastatic process.

Animals↗

PubMed1996

The carbohydrate N-acetylglucosamine is involved in the guidance of neurites from chick ciliary ganglion neurons through the extracellular matrix of rat skeletal muscle fiber.

In the present work we study the functional role of muscle cell extracellular matrix components in axonal guidance during synaptic regeneration. We focused on components recognized by the N-acetylglucosamine-specific lectin called wheat germ agglutinin (WGA) that has been shown to bind to the muscle cell extracellular matrix. We have used a cryoculture bioassay which is based on the ability of chick ciliary ganglion neurons to grow on rat skeletal muscle cryostat sections [Covault, J., et al., J. Neurosci., 105 (1987) 2479-2488.]. In control cultures neurites extended upon the muscle sections closely associated to the muscle cell surface. Masking WGA lectin receptors on the muscle cell surface perturbed the behavior of neurites. On WGA-treated sections, most of the neurites extended indiscriminately on intercellular and intracellular regions. These results indicate that N-acetylglucosamine-bearing molecules on muscle cell surfaces may play functional roles in the guidance of neurites through the extracellular matrix.

Acetylglucosamine↗

PubMed1996

Characteristics of high and low laminin-adherent Dunn osteosarcoma cells selected by adhesiveness to laminin. Correlation between invasiveness through the extracellular matrix and pulmonary metastatic potential.

We investigated the invasiveness through the extracellular matrix and pulmonary metastatic potential in high laminin-adherent [LN(+)] and low laminin-adherent [LN(-)] Dunn oseosarcoma cells selected for adhesiveness to laminin. In the invasion assay using a reconstituted basement membrane (matrigel) in a Boyden chamber, LN(+) cells proved to be more invasive than LN(-) and the parental Dunn cells. Pulmonary metastatic potential was correlated with invasiveness through the matrigel in three cell types. The ability of LN(+) cells to attach to laminin and the matrigel was significantly higher than that of LN(-) or the parental Dunn cells. LN(-) cells showed much lower attachment ability compared to the other cells. There were no significant differences in type IV collagenolysis and cell migration among the three cell types. In LN(+) and the parental Dunn cells, laminin significantly stimulated type IV collagenolytic and migration activities. LN(-) cells showed no significant differences of type IV collagenolysis and cell migration in response to laminin. These findings suggested that the different invasiveness of these cells was associated with the difference in the abilities of cell attachment to laminin and type IV collagenolysis and cell migration activities stimulated by laminin. YIGSR inhibited not only the laminin-mediated cell attachment but also the type IV collagenolysis and cell migration induced by the cell attachment to laminin. The amount of laminin receptor of LN(+) cells was about fourfold that of LN(-) and twofold that of the parental Dunn cells, suggesting the stimulatory effect of laminin on the invasiveness through the matrix is associated with the level of laminin receptor expression in these cells. The present study provides several findings suggesting that laminin has important roles in invasiveness through the extracellular matrix and metastasis formation in Dunn osteosarcoma cells.

Animals↗

PubMed1988

Extracellular matrix alterations during endochondral ossification in humans.

Immunohistochemical methods were employed to examine alterations in the cartilage extracellular matrix constituents associated with endochondral ossification in humans. The distributions of chondroitin 4- and 6-sulfate and keratan sulfate proteoglycan (PG) determinants, cartilage PG link protein, collagen types I and II, and fibronectin were determined in iliac crest growth-plate specimens using the avidin-biotin-horseradish peroxidase system. Collagen type II was distributed throughout the growth plate, providing a framework within which chondrocytes divided and formed clusters of differentiating (hypertrophic) cells. The septa between these clusters and their subchondral extensions into underlying bone trabeculae were rich in PG, PG link protein, and collagen type II and resembled the extracellular matrix of reserve cartilage. The territorial matrix associated with the differentiating cells within the clusters contained reduced amounts of collagen type II, PG link protein, and possibly cartilage PG. Collagen type I and fibronectin were detected within the cytoplasm of the maturing and degenerating cells, and fibronectin localized intensely to the pericellular matrix envelopes of these cells. These alterations presumably facilitate the degradation of the matrix associated with the cell clusters by invading vascular tissue, while the septa, which retain the characteristics of more typical cartilage matrix, are not degraded and firmly anchor the cartilage to the subchondral bone.

Adolescent↗