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Results for “Extracellular Matrix”

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PubMed1991

Attachment characteristics of bovine bronchial epithelial cells to extracellular matrix components.

Attachment of cells to extracellular matrix (ECM) plays an important role in the regulation of cell growth and differentiated function. We hypothesized that bronchial epithelial cells preferentially attach to ECM proteins and utilize specific receptors for ECM proteins. Bronchial epithelial cells were obtained from bovine lung by protease digestion. Both freshly isolated and cultured bronchial epithelial cells were plated onto plastic petri dishes coated with bovine serum albumin, type I collagen, type IV collagen, fibronectin, laminin, ECM synthesized by cultured bronchial epithelial cells, or uncoated. Freshly isolated cells demonstrated significant attachment to ECM but weak attachment to other matrix proteins. Cultured bronchial epithelial cells attached well to ECM; however, they had relatively increased attachment to type I collagen, type IV collagen, fibronectin, and laminin compared to freshly isolated cells. To determine whether the attachment of bronchial epithelial cells is arginine-glycine-aspartic acid (RGD)-mediated, an RGD-containing peptide known to block attachment mediated by many integrin receptors was added to the media (400 micrograms/ml). There was no inhibition of attachment of freshly isolated cells; however, there was significant but not complete inhibition of the attachment of the cultured cells to type IV collagen, laminin, and fibronectin, but not to type I collagen or ECM. Thus, freshly isolated bronchial epithelial cells readily adhere to ECM, and the attachment does not appear to be mediated by RGD-dependent receptors. Cultured bronchial epithelial cells demonstrate increased attachment to component proteins of ECM, and this attachment is, in part, to RGD-dependent receptors.

Animals↗

PubMed1999

Specific interactions between Porphyromonas gingivalis fimbriae and human extracellular matrix proteins.

The interactions of the extracellular matrix (ECM) proteins (laminin, elastin, fibronectin, type I collagen, thrombospondin and vitronectin) with the fimbriae of Porphyromonas gingivalis were analyzed based on surface plasmon resonance (SPR) spectroscopy using a biomolecular interaction analyzing system (BIAcore). The BIAcore profiles demonstrated that fimbriae specifically bound to all of the ECM proteins with significant association constants (Ka). Vitronectin showed the highest affinity to fimbriae (Ka = 3.79 x 10(6) M-1), while the affinity of laminin was lowest (Ka = 2.15 x 10(6) M-1). A synthetic peptide which is a potent inhibitor of fimbrial binding to salivary proteins was not significantly effective on the fimbrial interactions with the ECM proteins. Using polystyrene microtiter plates revealed that P. gingivalis fimbriae bound markedly to immobilized fibronectin and type I collagen, while the interaction of fimbriae with the other ECM proteins was not clearly demonstrated. These results suggest that interactions between fimbriae and the ECM proteins occur with specific affinities which are not mediated by mechanisms identical to those of salivary proteins. It was also shown that SPR spectroscopy is a useful method to analyze these specific interactions.

Animals↗

PubMed1985

Morphological and functional effects of extracellular matrix on pancreatic islet cell cultures.

Extracellular matrix (ECM) has been reported to enhance epithelial cell attachment and proliferation as well as to induce differentiation in vitro. In an attempt to determine the benefits of culturing pancreatic islet cells on ECM, we studied the morphological and functional patterns of rat islet cells and an insulin-secreting tumor cell line. ECM enhanced islet cell attachment and proliferation when compared to plastic, as suggested by a higher specific activity of DNA synthesis and a higher mitotic index. Cells on ECM were heterogeneous in size and insulin content. They showed extended areas of confluence. Cultures on plastic demonstrated an organisation in clusters and low mitotic activity. However, ECM did not allow for reconstitution of an islet-like structure. When compared to plastic, an initial decrease in basal and stimulated insulin secretion per million cells was observed on ECM, but B-cell activity was restored after 6 days of culture. Glucagon and somatostatin secretion were similar on both substrates. These data suggest that ECM enhances markedly islet cells attachment and proliferation, as well as long-term culture maintenance.

Animals↗

PubMed1991

Rat chromosome 5 (q22-23) contains elements that control cell morphology and interactions with the extracellular matrix: a study of normal fibroblast x malignant hepatoma cell hybrids.

Cell interactions with the extracellular matrix are consistently modified in neoplasia. Malignant transformation has been correlated with modifications in the synthesis and distribution of matrix components and with alterations of cell adhesive properties to these components. A particular class of genes, able to suppress the transformed phenotype in normal cells, may be involved in those phenotypic changes. By studying somatic cell hybrids between mouse hepatoma (BWTG3) cells and normal rat skin fibroblasts (RSF), Islam and co-workers were able to localize a gene or a group of genes controlling anchorage dependence and cell growth in vitro. This (or these) gene(s) was (were) assigned to the q22-23 fragment of rat chromosome 5. In the present study, we compare the morphology and the interactions with the extracellular matrix proteins (laminin, fibronectin, and collagen IV) and the synthesis of these proteins by RSF X BWTG3 hybrid cells that had either retained (BS181p10) or lost (BS181a5) the q22-23 region of rat chromosome 5. Our results suggest that the rat 5q22-23 fragment controls a part of the cell differentiation program including morphology, attachment to extracellular matrix, and synthesis of some matrix proteins, particularly alpha 1 and alpha 2 chains of collagen IV.

Animals↗

PubMed2003

A bit of give and take: the relationship between the extracellular matrix and the developing chondrocyte.

The extracellular matrix (ECM), once thought to be a static structural component of tissues, is now known to play a complex and dynamic role in a variety of cellular functions in a number of diverse tissues. A significant body of literature attests to the ability of the ECM to communicate both spatial and temporal information to adherent cells, thereby directing cell behavior via interactions between the ECM and cell-surface receptors. Moreover, volumes of experimental data show that a great deal of communication travels in the opposite direction, from the cell to the ECM, allowing for regulation of the cues transmitted by the ECM. As such, the ECM, with respect to its components and their organization, is not a fixed reflection of the state the local microenvironment in which a cell finds itself at a particular time, but rather is able to respond to and effect changes in its local microenvironment. As an example of the developmental consequences of ECM interactions, this review gives an overview of the 'give and take' relationship between the ECM and the cells of the developing skeletal elements, in particular, the chondrocyte.

Animals↗

PubMed1993

Effects of extracellular matrix components on cell locomotion.

The extracellular matrix (ecm), which is composed of collagens, glycoproteins, and proteoglycans, has emerged as an important regulator of cell locomotion. This review describes some of the mechanisms by which the ecm may regulate locomotion, focusing primarily on cell extension and lamellae formation. Ecm-receptor interactions form an important part of cell recognition of ecm. Such interactions can result in altered cell adhesion, signal transduction, and cytoskeletal organization, all of which impact on cell locomotion. It is important to note that although the effects of single ecm components have been studied, generally, the cell is likely to perceive ecm in vivo as a macromolecular complex. It will fall to future work to define how complexes of ecm regulate cell behavior. Because of our own particular research bias, we focus on reviewing the role of fibronectin, integrins, chondroitin sulfate, hyaluronan, and hyaluronan receptors in the regulation of cell locomotion and examine their effect on adhesion, signal transduction, and cytoskeletal integrity. Cytoskeleton assembly mechanisms, particularly those that might be regulated by the ecm, are also described. These events are summarized in a working model of ecm-promoted locomotion.

Animals↗

PubMed1995

Extracellular matrix and its receptors during development.

Extracellular matrix (ECM) components are essential for morphogenesis of virtually all tissues. The ECM interacts with the cell surface by binding to specific receptors. The first family of receptors for the ECM that was identified was the integrin family. Integrins are composed of an alpha and a beta-chain, both of which are single pass transmembrane proteins. In muscle cells the dystroglycan complex forms another important receptor system for ECM. It is a complex composed of many proteins. Recent studies have shown that dystroglycan is expressed by embryonic epithelial cells as well. The nature of constituents of the dystroglycan complex is well known for muscle, whereas the detailed composition of the dystroglycan complex in embryonic epithelium is not yet well known. We here review the evidence that binding of ECM to integrins and the dystroglycan complex could be essential for muscle and epithelial cell development and function. It is likely that integrins and the dystroglycan complex have distinct roles during development. It will be an interesting task to study the signal transduction pathways elicited by the interactions between ECM and the two receptor systems during muscle and epithelial morphogenesis.

Animals↗

PubMed2004

The role of extracellular matrix protein 1 in human skin.

Extracellular matrix protein 1 (ECM1) was first identified in 1994 as an 85-kDa glycoprotein secreted by a mouse osteogenic stromal cell line. Subsequently, the human homologue has been found to regulate endochondral bone formation, and to stimulate proliferation of endothelial cells and induce angiogenesis. However, a role for ECM1 in skin physiology and homeostasis has also emerged. Specifically, in 2002, loss-of-function mutations in the ECM1 gene were discovered to be the cause of the rare autosomal recessive genodermatosis, lipoid proteinosis. This inherited disorder is characterized clinically by skin and mucosal infiltration and scarring and histologically by disruption/duplication of basement membrane and widespread deposition of hyaline material in the dermis. Moreover, other recent studies have identified circulating autoantibodies against the ECM1 protein in most patients with lichen sclerosus, a common chronic inflammatory condition that shares some clinicopathological features with lipoid proteinosis. ECM1 thus serves as a target antigen in both an inherited and an acquired skin disorder. Within the epidermis, ECM1 has a role in the control of keratinocyte differentiation. Within the dermis, ECM1 binds to the major heparan sulphate proteoglycan, perlecan. In this way, ECM1 may act as a "biological glue" in the dermis, helping to regulate basement membrane and interstitial collagen fibril macro-assembly and growth factor binding. ECM1 may also have a role in other acquired skin disorders and physiological skin changes including scarring, wound healing and skin ageing, although this remains to be determined.

Cell Division↗

PubMed1996

A two-domain mechanism for group A streptococcal adherence through protein F to the extracellular matrix.

Streptococcus pyogenes binds to the extracellular matrix (ECM) and a variety of host cells and tissues, causing diverse human diseases. Protein F, a S.pyogenes adhesin that binds fibronectin (Fn), contains two binding domains. A repeated domain (RD2) and an additional domain (UR), located immediately N-terminal to RD2. Both domains are required for maximal Fn binding. In this study, we characterize RD2 and UR precisely and compare their functions and binding sites in Fn. The minimal functional unit of RD2 is of 44 amino acids, with contributions from two adjacent RD2 repeats flanked by a novel 'MGGQSES' motif. RD2 binds to the N-terminal fibrin binding domain of Fn. UR contains 49 amino acids, of which six are from the first repeat of RD2. It binds to Fn with higher affinity than RD2, and recognizes a larger fragment that contains fibrin and collagen binding domains. Expression of UR and RD2 independently on the surface-exposed region of unrelated streptococcal protein demonstrates that both mediate adherence of the bacteria to the ECM. We describe here a mechanism of adherence of a pathogen that involves two pairs of sites located on a single adhesin molecule and directed at the same host receptor.

Adhesins, Bacterial↗

PubMed1990

Extracellular matrix receptors in the kidney cortex.

Extracellular matrix (ECM) receptors anchor cells to substratum and impart positional information to cells. Within the group of ECM receptors known as integrins, alpha-subunits of these alpha beta heterodimers define ligand specificity, whereas beta-subunits define the subclass. We used immunofluorescence with anti-ECM receptor antibodies to examine distribution within human kidney cortex of all known alpha-subunits in the beta 1 subclass of integrins as well as a non-integrin 67-kDa elastin/lamin receptor. The alpha 1-subunit (alpha 1 beta 1 defines a collagen receptor) was present in mesangium and base of all tubule epithelial cells; alpha 2 (collagen) was present in mesangium and in distal but not proximal tubule cells; alpha 3 (collagen, laminin, fibronectin) was diffusely distributed within glomeruli but tubule staining was less intense; alpha 4 (fibronectin) was absent; alpha 5 (fibronectin) was present in blood vessels; and alpha 6 (laminin) was present along basolateral aspect of all tubule cells but absent in glomeruli. The elastin/laminin receptor was present in all tubule epithelial cells, but staining was heavier in distal tubules, especially intercalated cells. Thus striking heterogeneity in ECM receptor distribution was noted. For collagen receptors, differences in tubule staining were pronounced. Despite the presence of laminin within both glomeruli and tubules, laminin receptors also showed marked differences in staining between these structures. Both differences in ECM structure and intrinsic differences among different cells may underlie these differences in ECM receptor distribution.

Collagen↗

PubMed2004

Local, three-dimensional strain measurements within largely deformed extracellular matrix constructs.

The ability to create extracellular matrix (ECM) constructs that are mechanically and biochemically similar to those found in vivo and to understand how their properties affect cellular responses will drive the next generation of tissue engineering strategies. To date, many mechanisms by which cells biochemically communicate with the ECM are known. However the mechanisms by which mechanical information is transmitted between cells and their ECM remain to be elucidated. "Self-assembled" collagen matrices provide an in vitro-model system to study the mechanical behavior of ECM. To begin to understand how the ECM and the cells interact mechanically, the three-dimensional (3D) mechanical properties of the ECM must be quantified at the micro-(local) level in addition to information measured at the macro-(global) level. Here we describe an incremental digital volume correlation (IDVC) algorithm to quantify large (>0.05) 3D mechanical strains in the microstructure of 3D collagen matrices in response to applied mechanical loads. Strain measurements from the IDVC algorithm rely on 3D confocal images acquired from collagen matrices under applied mechanical loads. The accuracy and the precision of the IDVC algorithm was verified by comparing both image volumes collected in succession when no deformation was applied to the ECM (zero strain) and image volumes to which simulated deformations were applied in both ID and 3D (simulated strains). Results indicate that the IDVC algorithm can accurately and precisely determine the 3D strain state inside largely deformed collagen ECMs. Finally, the usefulness of the algorithm was demonstrated by measuring the microlevel 3D strain response of a collagen ECM loaded in tension.

Anisotropy↗

PubMed2005

Tissue-engineered myocardial patch derived from extracellular matrix provides regional mechanical function.

BACKGROUND: Extracellular matrix (ECM), a tissue-engineered scaffold, recently demonstrated cardiomyocyte population after myocardial implantation. Surgical restoration of myocardium frequently uses Dacron as a myocardial patch. We hypothesized that an ECM-derived myocardial patch would provide a mechanical benefit not seen with Dacron. METHODS AND RESULTS: Using a canine model, a full thickness defect in the right ventricle was repaired with either Dacron or ECM. A third group had no surgery and determined baseline RV function. Eight weeks later, global systolic function was assessed by the preload recruitable stroke work relationship. Regional systolic function was measured by systolic area contraction (SAC), calculated by high density mechanical mapping. Tau was used to assess global diastolic function. Recoil rate and diastolic shear were used as measures of regional diastolic function. After functional data acquisition, tissue was fixed for histological evaluation. Global systolic and diastolic functions were similar at baseline and after ECM and Dacron implantation. Regional systolic function was greater in the ECM group compared with the Dacron group (SAC: 4.1+/-0.9% versus -1.8+/-1.1, P<0.05). Regional diastolic function was also greater in the ECM group (recoil rate (degrees sec(-1)): -44+/-7 versus -17+/-2, ECM versus Dacron; P<0.05). Immunohistochemical analysis revealed cardiomyocytes in the ECM implant region, a finding not seen with Dacron. CONCLUSIONS: At 8 weeks, an ECM-derived tissue-engineered myocardial patch provides regional mechanical function, likely related to cardiomyocyte population. These results are in sharp contrast to Dacron, a commonly used myocardial patch.

Absorbable Implants↗

PubMed2002

Extracellular matrix oxidation modulates survival, NF-kappaB translocation, and MAPK activity in mesangial cells.

Inflammatory injury to the kidney may oxidize extracellular matrix proteins. These changes appear to impair adhesion of glomerular mesangial cells and might impact signaling mechanisms in these cells. In this study we evaluated how extracellular matrix oxidation could modulate the development of apoptosis as well as the activity of the transcription factor NF-kappaB and that of the MAPK family members ERK-1,2 and JNK. Exposure of mesangial cells to oxidized matrix enhanced the percentage of apoptotic cells. Western blot analysis revealed diminished levels of the phosphorylated form of ERK-1,2 in cells on oxidized matrix, while levels of phosphorylated JNK were increased. Cells on unmodified matrix were found to have rapid translocation of the p65 subunit of NF-kappaB, which was attenuated in cells on oxidized matrix. These findings suggest that extracellular matrix oxidation may impair survival of mesangial cells in association with decreased levels of pERK-1,2, increased levels of pJNK, and diminished nuclear translocation of the transcription factor NF-kappaB.

Active Transport, Cell Nucleus↗

PubMed1992

Extracellular matrix formation by epithelial cells from human polycystic kidney cysts in culture.

Cells from the cysts of patients with autosomal dominant polycystic kidney disease (PKD) were grown in vitro under standard conditions without the aid of collagen-pretreated surfaces, and both the synthesis and composition of the extracellular matrix were investigated. At confluence, PKD cells presented the typical features of epithelial cells, but showed a different collagen composition from fibroblasts. Compared with normal tubular epithelia (NTE), PKD monolayers produced an excess of extracellular matrix, which accounted for 30% of the total incorporation of [3H] proline, although this value was considerably lower (by a factor of 10) in the case of NTE. Immunohistochemical and electrophoretic techniques revealed a complex collagen composition in the extracellular matrix which included [alpha (III)]3 and collagen IV. However, part of the collagen components remained unidentified in spite of the fact that they exhibited a typical M(r) of alpha 1(I) and alpha 2(I) in the presence of urea. Immunoprecipitation with monospecific antibodies and Northern blotting with specific probes failed to recognize alpha 1(I) and alpha 2(I), but demonstrated their presence in fibroblasts. Purification and cyanogen bromide digestion demonstrated a strong interhomology in fingerprint peptide composition among the uncharacterized collagens synthesized by PKD cells, thus suggesting a common identity. These observations document a markedly augmented production of extracellular matrix by PKD cultured cells in vitro, and show the presence of collagens which do not share homologies with the major collagen molecules. A better characterization of extracellular matrix composition is central to any comprehension of the cytogenetic mechanisms in vivo.

Adult↗

PubMed1988

Localization of protease nexin-1 on the fibroblast extracellular matrix.

Protease nexin-1 (PN-1) is a protease inhibitor that is secreted by fibroblasts and several other cultured cells. PN-1 forms complexes with certain serine proteases in the extracellular environment including thrombin, urokinase, and plasmin. The complexes then bind to the cells and are rapidly internalized and degraded. This report demonstrates that PN-1 is present on the surface of fibroblasts, bound to the extracellular matrix. Immunofluorescent studies showed that PN-1 colocalized with fibronectin on both intact cells and in preparations of extracellular matrix made from these cells. In contrast, PN-1 did not colocalize with the epidermal growth factor receptor, a plasma membrane marker. An enzyme-lined immunosorbent assay was developed which showed that the extracellular matrix contained at least 60-80% of the cellular immunoreactive PN-1. Extraction of the matrix with 2 M NaCl removed PN-1 in a form which reacted with 125I-thrombin to form complexes which were immunoprecipitated by anti-PN-1 IgG and were of identical size as complexes made from soluble PN-1 and 125I-thrombin. These data indicate that in addition to its role as a soluble protease inhibitor, PN-1 is also a component of the extracellular matrix and might control its proteolysis.

Amyloid beta-Protein Precursor↗

PubMed2001

Synthesis and degradation of basement membranes and extracellular matrix and their regulation by TGF-beta in invasive carcinomas (Review).

The proper structure of the extracellular matrix, in particular of the basement membrane and the adjacent interstitial matrix, are essential prerequisites for a proper function of tissues. Invasive growth in malignant tumors is associated with a destruction of various matrix structures. Due to extensive recent analyses significant advances have been made in the knowledge of the structure of the extracellular matrix, the composition of its most important constituents, their metabolism and that of matrix degrading enzymes. This information provides insight into the pathophysiology of malignant growth. Thereby, it has been shown that malignant tumor growth is associated with a loss of basement membrane (BM) material which, however, disappears not homogeneously, but affects various BM components to different degree. The loss of an intact BM as the first barrier is therefore the initial step of tumor invasion. Despite this loss there is evidence that the de novo synthesis of BM constituents in tumor and adjacent stromal cells is enhanced. Thus, it is obvious that BM material is degraded during the invasion process to significant degree. In addition, since there is a positive correlation between the amount of retained peritumoral BM and a higher degree of tumor cell differentiation the amount of retained BM material seems to represent a marker for the biological behaviour of the tumor cells. The loss of BM material is well explained by a significant expression of major matrix degrading enzymes, the matrix metalloproteinases (MMPs) both on the mRNA and protein level. Here again, there is considerable data indicating that both tumor and stroma cells are involved in the MMP synthesis. In addition to the loss of BM substances, the interstitial extracellular matrix (ECM) is disarranged. This disarrangement may comprise enhanced de novo synthesis ("desmoplasia") or dissolution by distinct MMPs (collagenases, such as MMP-1) reflecting obviously different reaction statuses of the stromal cells. Finally, significant work has been done on the elucidation of the role of regulating cytokine systems. To this regard, particular attention has been paid to the TGF-beta system and it has been shown that the major three isoforms of TGF-betas are upregulated both in tumor and stroma cells. Since the TGF-beta-effect is mainly mediated by a particular signalling system via the TGF-beta-receptors (TBRs), the investigation of this system has provided considerable insight into the role of TBRs which are now known to represent the most potent tumor suppressor genes. Thus frequent mutations in the TBR-II gene, one of the three TBRs, in various carcinomas suggest that these molecular alterations are responsible for both the loss of the control of cellular proliferation (in tumor cells) and altered matrix metabolism (in tumor and stroma cells). The further analysis of this major cytokine system therefore will provide us with major insights into the molecular abnormalities of invasive tumor growth.

Basement Membrane↗

PubMed1987

Perturbation of human endothelial cells by thrombin or PMA changes the reactivity of their extracellular matrix towards platelets.

In this study we have examined the influence of perturbation of endothelial cells on the amounts of fibronectin and von Willebrand factor in their extracellular matrix and the consequences of a changed composition of the matrix on platelet adhesion. For this purpose, we have used an in vitro perfusion system with which we can investigate the interactions of platelets in flowing blood with cultured endothelial cells and their extracellular matrix (Sakariassen, K. S., P. A. M. M. Aarts, P. G. de Groot, W. P. M. Houdgk, and J. J. Sixma, 1983, J. Lab. Clin Med. 102:522-535). Treatment of endothelial cells with 0.1-1.0 U/ml thrombin for 2 h increased the reactivity of the extracellular matrix, isolated after the thrombin treatment, towards platelets by approximately 50%. The increased reactivity did not depend on de novo protein synthesis but was inhibited by 3-deazaadenosine, an inhibitor of phospholipid methylation, which also inhibits the stimulus-induced instantaneous release of von Willebrand factor from endothelial cells. However, no changes in the amounts of von Willebrand factor and fibronectin in the matrix were detected. Thrombin may change the organization of the matrix proteins, not the composition. When endothelial cells were perturbed with the phorbol ester PMA or thrombin for 3 d, the adhesion of platelets to the extracellular matrix of treated cells was strongly impaired. This impairment coincided with a decrease in the amounts of von Willebrand factor and fibronectin present in the matrix. These results indicate that, after perturbation, endothelial cells regulate the composition of their matrix, and that this regulation has consequences for the adhesion of platelets.

Blood Platelets↗

PubMed1992

Chondroitin sulfate in the extracellular matrix of the medial and lateral superior olivary nuclei in the dog.

Chondroitin sulfate was examined in the extracellular matrix of the canine medial and lateral superior olivary nuclei by light and electron microscopic immunocytochemistry. The extracellular matrix around the large neurons was intensely stained with a monoclonal antibody recognizing D-glucuronic acid 2-sulfate----N-acetylgalactosamine 6-sulfate (D-unit) and this staining degree was remarkably reduced after chondroitinase ABC digestion. Neuronal cytoplasm, glial cells or capillaries in these nuclei were not stained with the monoclonal antibody. The results indicate the presence of disaccharide residue of D-glucuronic acid 2-sulfate----N-acetylgalactosamine 6-sulfate in the chondroitin sulfate proteoglycan of the extracellular matrix.

Animals↗