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 307 records · Page 17Linked to original sources

PubMed2002

Epithelial repair: roles of extracellular matrix.

PURPOSE: To review studies of the roles of extracellular matrix (ECM) metabolism in corneal epithelium during wound repair. Methods. 1) Alterations in the structure and composition of epithelial basement membrane during corneal epithelial healing were examined histologically and immunohistochemically. 2) The effects of procollagen and hyaluronan synthesis inhibitors on the spread of rabbit corneal epithelium were determined in organ culture. 3) Expression of keratan sulfate proteoglycan (KSPG) proteins in corneal epithelium was examined during repair after injury in wild-type and lumican-null mice. RESULTS: 1) Corneal epithelial basement membrane was transiently degraded and reassembled during tissue repair. Patterns of type IV collagen immunoreactivity were also transiently altered. The system of matrix metalloproteinase-tissue inhibitors of metalloproteinases may play an important role in the disassembly and reorganization of epithelial basement membrane. 2) Inhibitors of procollagen secretion and hyaluronan biosynthesis disrupted the spread of a corneal epithelial sheet in situ. 3) Among the corneal KSPG proteins examined, lumican was transiently expressed in migrating murine corneal epithelial cells. Anti-lumican antibody inhibited corneal epithelial resurfacing in organ culture. The absence of lumican was found to delay corneal epithelial wound healing in mice. CONCLUSION: Extracellular matrix metabolism by the injured corneal epithelium is important in the repair process.

Animals↗

PubMed1992

Collaborative interactions between growth factors and the extracellular matrix.

The contribution of extracellular matrix (ECM) components to the regulation of cell adhesion, proliferation and differentiation is receiving much attention. Recently, it has become evident that certain cellular responses require the combined action of ECM components and soluble growth factors. This article examines possible mechanisms underlying the synergistic interactions of growth factors and the ECM.

Journal Article↗

PubMed2001

Cell adhesion and migration properties of beta 2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation.

Regulated adhesion of leukocytes to the extracellular matrix is essential for transmigration of blood vessels and subsequent migration into the stroma of inflamed tissues. Although beta(2)-integrins play an indisputable role in adhesion of polymorphonuclear granulocytes (PMN) to endothelium, we show here that beta(1)- and beta(3)-integrins but not beta(2)-integrin are essential for the adhesion to and migration on extracellular matrix molecules of the endothelial cell basement membrane and subjacent interstitial matrix. Mouse wild type and beta(2)-integrin null PMN and the progranulocytic cell line 32DC13 were employed in in vitro adhesion and migration assays using extracellular matrix molecules expressed at sites of extravasation in vivo, in particular the endothelial cell laminins 8 and 10. Wild type and beta(2)-integrin null PMN showed the same pattern of ECM binding, indicating that beta(2)-integrins do not mediate specific adhesion of PMN to the extracellular matrix molecules tested; binding was observed to the interstitial matrix molecules, fibronectin and vitronectin, via integrins alpha(5)beta(1) and alpha(v)beta(3), respectively; to laminin 10 via alpha(6)beta(1); but not to laminins 1, 2, and 8, collagen type I and IV, perlecan, or tenascin-C. PMN binding to laminins 1, 2, and 8 could not be induced despite surface expression of functionally active integrin alpha(6)beta(1), a major laminin receptor, demonstrating that expression of alpha(6)beta(1) alone is insufficient for ligand binding and suggesting the involvement of accessory factors. Nevertheless, laminins 1, 8, and 10 supported PMN migration, indicating that differential cellular signaling via laminins is independent of the extent of adhesion. The data demonstrate that adhesive and nonadhesive interactions with components of the endothelial cell basement membrane and subjacent interstitium play decisive roles in controlling PMN movement into sites of inflammation and illustrate that beta(2)-integrins are not essential for such interactions.

Animals↗

PubMed1997

Reattachment of cultured human retinal pigment epithelium to extracellular matrix and human Bruch's membrane.

PURPOSE: To determine the mechanism of reattachment of harvested human retinal pigment epithelium (RPE) to RPE-derived extracellular matrix and Bruch's membrane. METHODS: Confluent first-to third-passage human RPE were harvested from tissue culture and plated onto RPE-derived extracellular matrix or human Bruch's membrane exoplants denuded of cells by treatment with 0.02 N ammonium hydroxide. The authors measured RPE reattachment to uncoated surfaces or surfaces precoated with extracellular matrix proteins (fibronectin, laminin, vitronectin, or type IV collagen), antibodies to extracellular matrix-proteins, or the synthetic peptide RGDS (arginine-glycine-aspartate-serine). Some RPE were pretreated with anti-beta 1 integrin antibodies before plating onto either substrate. RESULTS: Coating the surface of either RPE-derived extracellular matrix or Bruch's membrane with fibronectin, laminin, vitronectin, or type IV collagen increased the RPE attachment rate. Exposing RPE to anti-beta 1 integrin antibodies or RGDS or precoating the surface with antibodies to fibronectin, laminin, vitronectin, or type IV collagen decreased the RPE attachment rate to both surfaces. The RPE attachment rate to Bruch's membrane was lower when the exoplants were harvested from the macula of older (age, 70 to 90 years) versus younger (age, 30 to 40 years) persons (52.4 +/- 3.6% versus 64.3 +/- 3.5%, respectively; P < 0.05). CONCLUSIONS: The attachment of cultured human RPE cells to human Bruch's membrane or to RPE-derived extracellular matrix is mediated by an interaction between the beta 1-subunit of integrin on the RPE surface and ligands in the extracellular matrix that include laminin, fibronectin, vitronectin, and type IV collagen. The lower rate of RPE reattachment to the macula from older human cadaveric eyes may have implications for studies aimed at RPE transplantation in elderly persons.

Adhesiveness↗

PubMed2000

Morphogenetic messages are in the extracellular matrix: biotechnology from bench to bedside.

The origin and evolution of multicellular metazoa was accompanied by the appearance of extracellular matrix. The demineralized extracellular matrix of bone is enriched in morphogenetic proteins that induce bone. Bone morphogenetic proteins (BMPs) are intimately bound to collagens. BMP-4 has high affinity for type-IV collagen, and other binding proteins such as noggin and chordin. Soluble morphogens are kept in the solid state by extracellular matrix. In this sense Nature used the principles of affinity matrices long before humans patented the principle of affinity chromatography.

Animals↗

PubMed2002

Stromal extracellular matrix reduces chemotherapy-induced apoptosis in colon cancer cell lines.

Several studies have shown that extracellular matrix reduces chemotherapeutic drugs-induced apoptosis in small cell lung cancer cells, myelomas and gliomas. We have investigated the protective effect of defined extracellular matrix components and of extracellular matrix from different cell types (fibroblasts, hepatocytes and intestinal epithelial cells) on the toxicity of three types of chemotherapeutic drugs on colon cancer cells. Human colon cancer cell lines LS174T and LiM6 were plated on plastic, on hepatocyte-derived ECM or on stromal ECM and in the presence of the antimetabolite 5-fluorouracil (5-FU). the topoisomerase I inhibitor camptothecin and the topoisomerase II inhibitor etoposide. We determined IC50 for the drugs for each of these culture conditions. We also determined the expression of the anti-apoptotic proteins bcl-2 and bcl-x (L) under these culture conditions. We found that stromal ECM protected LiM6 cells from the toxicity of etoposide and LS174T, but not LiM6 cells, from the toxicity of camptothecin. Collagen 1, fibronectin and fibroblast-derived ECM rendered LiM6 cells, but not LS174T, more sensitive to the harmful effect of 5-FU. Both colon cell lines had increased expression of anti-apoptotic proteins bcl-2 and bcl-x(L) when cultured on the various ECMs and with the drugs, but there was no correlation between a protective ECM effect and expression of the anti-apoptotic proteins. Stromal-derived ECM may protect colon cancer cells from etoposide and camptothecin-induced apotosis, through a mechanism that is not bcl-2 or bcl-x(L) dependant.

Adenocarcinoma↗

PubMed2005

Extracellular matrix alterations in brains lacking four of its components.

The organization of the brain extracellular matrix appears to be based on aggregates of hyaluronan and proteoglycans, connected by oligomeric glycoproteins. Mild phenotypical consequences were reported from several mouse strains lacking components of this matrix such as neurocan, brevican, tenascin-R, and tenascin-C. To further challenge the flexibility of the extracellular matrix network of the brain, mice lacking all four brain extracellular matrix molecules were generated, which were found to be viable and fertile. Analysis of the brains of 1-month-old quadruple KO mice revealed increased protein levels of fibulin-1 and fibulin-2. Histochemical analysis showed an unusual parenchymal deposition of these fibulins. The quadruple KO mice also displayed obvious changes in the pattern of deposition of hyaluronan. Further, an almost quadruple knockout like extracellular environment was noticed in the brains of triple knockout mice lacking both tenascins and brevican, since these brains had strongly reduced levels of neurocan.

Animals↗

PubMed1990

Association between collagen and glycosaminoglycans is altered in dermal extracellular matrix of fetal Steel (Sld/Sld) mice.

Altered extracellular matrix produced by Steel mutant fetuses affects the pigmentation of neural crest cells in vitro (K. Morrison-Graham, L. West-Johnsrud, and J.A. Weston, 1990, Dev. Biol. 139). Here, we demonstrate that collagen bundle morphology and hyaluronidase sensitivity of the glycosaminoglycans associated with the collagen fibrils differ between normal and mutant dermis. Although no differences were detected in the amounts of collagen or glycosaminoglycans produced in vitro or present in vivo, hyaluronic acid was more readily extracted from Sld/Sld than from normal skin. We suggest that the Steel mutation alters the organization of collagen bundles and associated hyaluronic acid within the extracellular matrix.

Animals↗

PubMed2001

[Trace elements and extracellular matrix].

OBJECTIVE: To investigate the effects of trace elements on the metabolism of extracellular matrix and explore the physiological and pathological mechanism of trauma. METHODS: Based on the experimental and clinical data, it was studied that the action of trace elements in the metabolism of extracellular matrix in trauma repairing. RESULTS: During wound healing, the trace elements were the components of many kinds of enzymes, carriers and proteins. They took part in the synthesis of hormones and vitamins as well as the transmission of information system. They activated many different kinds of enzymes and regulate the levels of free radicals. The trace elements had the complicated effects on the synthesis, decompose, deposition and reconstruction of collagen and other extracellular matrix. CONCLUSION: The trace elements play an important role in regulating the metabolism of extracellular matrix.

Collagen↗

PubMed1985

Alteration of the extracellular matrix of cultured human keratinocytes by transformation and during differentiation.

We have investigated the production of 3 extracellular matrix proteins (fibronectin, laminin and entactin) and glycosaminoglycans (GAGs) by keratinocytes derived from human squamous-cell carcinomas (SCCs). All the SCC lines retained the ability to synthesize fibronectin, laminin and entactin, and to incorporate them into an extracellular matrix. In some of the SCC lines fibronectin production was higher than in normal keratinocytes, and in most lines laminin production was equal to or higher than that seen in normal keratinocyte strains. All the tumorigenic SCC lines produced less entactin than normal keratinocytes. Five out of 7 SCC lines showed a shift in GAG production compared with normal keratinocytes, so that in these lines heparan sulphate was the major GAG as opposed to hyaluronic acid in the normal keratinocytes. As these changes could have been a consequence of the reduced differentiation found in the SCC lines, we fractionated normal keratinocytes into 4 size classes corresponding to different stages of differentiation, using Percoll gradient centrifugation. It was found that the ability to produce these extracellular matrix glycoproteins and GAGs was lost as keratinocytes terminally differentiated. However, this did not explain the matrix changes seen in the SCC lines, since the undifferentiated normal keratinocytes produced a normal pattern of extracellular matrix components. Nonetheless, the loss of extracellular matrix production may well explain the reduction in substratum adhesiveness which occurs as keratinocytes terminally differentiate.

Autoradiography↗

PubMed1998

Human cells unable to express decoron produced disorganized extracellular matrix lacking "shape modules" (interfibrillar proteoglycan bridges).

The shapes of extracellular matrices are determined by positioning collagen fibrils in the right places, oriented and maintained viv-à-vis each other. The fibrils are linked orthogonally by dermatan/chondroitin sulfates or keratan sulfate (in small proteoglycans) attached every approximately 65 nm via their protein moieties to collagen fibrils at specific binding sites. These regular repeating structures are the "shape modules." The characteristic arrays of orthogonal interfibrillar bridges were missing and the extracellular matrix was totally disorganized in matrices produced by fibroblasts taken postmortem from skin of an electively aborted fetus which did not express decoron in culture, thus supporting the shape module hypothesis. Biglycon, dermatan sulfate, heparan sulfate, collagen, and hyaluronan were produced by these cells but did not contribute to a normal extracellular matrix. A similar electron histochemical and biochemical survey of extracellular matrices produced by seven normal and eight osteogenesis imperfecta cell lines from donors of different ages and both sexes showed no comparable disruptions of their matrices. This investigation appears to be the first to demonstrate systematically proteoglycan:collagen interactions in matrices produced by cultured human cells.

Adult↗

PubMed1993

Therapeutic effects of danazol on endometrial cells may be activated by the presence of extracellular matrix.

OBJECTIVE: To demonstrate the direct effect of danazol on the endometrium in the presence of various types of extracellular matrix. STUDY DESIGN: Human endometrial cells (epithelial and stromal cells) were cultured over various extracellular matrix in the absence or presence of danazol. The effects of danazol on the growth of endometrial cells and the specific glandular structure were studied. RESULTS: Danazol (10(-7) mol/L) inhibited endometrial cell growth, and in the presence of Matrigel, the same danazol concentration demonstrated a stronger inhibitory effect on epithelial cell growth. Danazol inhibited the formation of the specific glandular structure. Its effect depended on the culture substrates used and was reversible. Danazol did not inhibit growth of cells cultured over type V collagen substrate, whereas growth of those grown over type IV collagen was greatly inhibited. CONCLUSION: The results indicate that a distinctive extracellular matrix around ectopic endometriotic tissue modulates cell growth and differentiation. Endometrium associated with a normal extracellular matrix is apparently protected from therapeutic drugs, whereas endometriotic tissue growing over a deranged extracellular matrix would be sensitive to therapeutic drugs, such as danazol.

Cell Differentiation↗

PubMed1990

Extracellular matrix in preneoplastic lesions and early cancer of the lung.

Characterization of preneoplastic lesions mainly concentrated on cellular, nuclear and epithelial atypias. The extracellular matrix was almost neglected, although malignant tumour cells interact with extracellular matrix molecules during tumour invasion. Until now systematic investigations of extracellular matrix components in preneoplastic lesions and early stages of lung cancer are lacking. 150 preneoplastic lesions, 10 specimens of early cancer and 30 specimens of normal bronchial mucosa were examined by means of immunofluorescence microscopy. The distribution of collagen type I and III and the non-collagenous glycoproteins laminin and fibronectin have been investigated by an indirect immunohistochemical method. With an increasing degree of preneoplasia an increased matrix disarrangement of the basement membrane zone could be observed. In severe dysplasia and carcinoma in situ neosynthesis of collagen type III and especially laminin in close association to neoangiogenesis could be demonstrated besides a disintegration of extracellular matrix components. In early lung cancer numerous laminin positive basement membrane like structures are situated around tumour cells. An enhanced deposition of collagen type I and III fibres could be demonstrated around tumour cell islets. The results indicate a partial loss of function in preneoplastic basal cells in cases of dysplasia and carcinoma in situ. In early stages of invasive squamous cell carcinoma of the bronchus, extracellular matrix components obviously could be produced by tumour cells.

Basement Membrane↗

PubMed1987

Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells.

The extracellular matrix secreted by cultured bovine smooth muscle cells (BSMC) contains an endothelial type plasminogen activator (PA) inhibitor. When PA is incubated with the matrix, a high molecular weight complex containing a truncated PA inhibitor is released into the supernatant. The inhibitor also dissociates from the matrix by treatment with glycine, pH 2.7, in its intact, functionally active, 45-kD form, whereas treatment of the matrix with thrombin results in the release of a cleaved, inactive, 41 kD PA inhibitor. Bowes melanoma cells but not smooth muscle cells cultured on BSMC matrices decrease available matrix associated PA inhibitor. PA inhibitor incorporated into the extracellular matrix may serve an important role in the regulation of plasminogen activator mediated matrix degradation.

Animals↗

PubMed1989

Immunolocalisation of extracellular matrix macromolecules in the rat spinal cord.

Extracellular matrix macromolecules are involved in many aspects of cell biology. The knowledge concerning the presence, the distribution and the role of these macromolecules in the central nervous system has not yet received sufficient attention. In the present work we studied by indirect immunohistochemical methods the localisation of five extracellular matrix macromolecules in the spinal cord of rats: three collagens: type I, type III, and type IV, and two structural glycoproteins: laminin and fibronectin. We found that all five macromolecules are present in the spinal cord of normal animals. They are localised exclusively in the connective type tissues: the meningeal sheets and the vascular walls. Only type I and type III collagens and fibronectin could be demonstrated around the epithelial cells of the ependyma.

Animals↗

PubMed2005

SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

Actins↗

PubMed2001

Blocking sp1 transcription factor broadly inhibits extracellular matrix gene expression in vitro and in vivo: implications for the treatment of tissue fibrosis.

Fibrosis is a consequence of injury characterized by accumulation of excess collagen and other extracellular matrix components, resulting in the destruction of normal tissue architecture and loss of function. Sp1 was originally described as a ubiquitous transcription factor. It is involved in the basal expression of extracellular matrix genes and may, therefore, be important in fibrotic processes. To evaluate the effect of Sp1 blockade on the expression of extracellular matrix genes, clones of NIH 3T3 fibroblasts stably transfected with an anti-sense Sp1 expression vector. Simultaneously reduced expression of several extracellular matrix genes as compared with mock-transfected clones was noted using differential hybridization of cDNA microarrays, without significant alteration in cell growth. Transfection of human dermal fibroblasts with several extracellular matrix gene (COL1A1, COL1A2, COL3A1, COL5A2, COL7A1, TIMP-1, and decorin) promoter/reporter constructs demonstrated that anti-sense Sp1-induced reduction of extracellular matrix gene mRNA steady-state levels results from transcriptional repression, consistent with the role of Sp1 as a transcription factor. Decoy Sp1 binding oligonucleotides inhibited COL1A2 promoter activity both in cultured fibroblasts and in vivo, in the skin of transgenic mice, which have integrated a mouse COL1A2 promoter/luciferase reporter gene construct. These results indicate that targeting Sp1 efficiently blocks extracellular matrix gene expression, and suggest that such an approach may represent an interesting therapeutic alternative toward the treatment of fibrotic disorders.

3T3 Cells↗

PubMed1995

Immunolocalization of extracellular matrix components in mixed tumors of the skin.

Mixed tumors of the skin are characterized by a proliferation of epithelial cells embedded in a mesenchymal matrix with a wide spectrum of histologic appearances. The characterization of the extracellular matrix components of mixed tumors of the skin has so far received little attention. We performed an immunohistochemical study of type IV collagen, laminin, fibronectin, and tenascin distribution in a series of 10 mixed tumors of the skin. Laminin localized at the basement membrane around solid epithelial nests and tubulo-alveolar structures, whereas type IV collagen, fibronectin, and tenascin were also expressed in the myxoid stroma. Tenascin and fibronectin localized in the chondroid matrix. The extracellular matrix components were prominently expressed in mixed tumors of the skin, suggesting that they could play an important role in the formation and organization of myxoid and chondroid matrices and in the epithelial-mesenchymal interactions of these tumors.

Adenoma, Pleomorphic↗