Journal articles: 'Extracellular matrix fragments'

1

McKeown-Longo, P. J., and D. F. Mosher. "Interaction of the 70,000-mol-wt amino-terminal fragment of fibronectin with the matrix-assembly receptor of fibroblasts." Journal of Cell Biology 100, no. 2 (February 1, 1985): 364–74. http://dx.doi.org/10.1083/jcb.100.2.364.

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Plasma fibronectin binds saturably and reversibly to substrate-attached fibroblasts and is subsequently incorporated into the extracellular matrix (McKeown-Longo, P.J., and D. F. Mosher, 1983, J. Cell Biol., 97:466-472). We examined whether fragments of fibronectin are processed in a similar way. The amino-terminal 70,000-mol-wt catheptic D fragment of fibronectin bound reversibly to cell surfaces with the same affinity as intact fibronectin but did not become incorporated into extracellular matrix. The 70,000-mol-wt fragment blocked binding of intact fibronectin to cell surfaces and incorporation of intact fibronectin into extracellular matrix. Binding of the 70,000-mol-wt fragment to cells was partially abolished by cleavage into 27,000-mol-wt heparin-binding and 40,000-mol-wt gelatin-binding fragments and more completely abolished by reduction and alkylation of disulfide bonds. Binding of the 70,000-mol-wt fragment to cells was not blocked by gelatin or heparin. When coated onto plastic, the 70,000-mol-wt fragment did not mediate attachment and spreading of suspended fibroblasts. Conversely, fibronectin fragments that had attachment and spreading activity did not block binding of exogenous fibronectin to substrate-attached cells. These results indicate that there is a cell binding site in the 70,000-mol-wt fragment that is distinct from the previously described cell attachment site and is required for assembly of exogenous fibronectin into extracellular matrix.

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Unsold, C., M. Hyytiainen, L. Bruckner-Tuderman, and J. Keski-Oja. "Latent TGF-beta binding protein LTBP-1 contains three potential extracellular matrix interacting domains." Journal of Cell Science 114, no. 1 (January 1, 2001): 187–97. http://dx.doi.org/10.1242/jcs.114.1.187.

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Latent TGF-beta binding proteins (LTBPs) are components of the extracellular matrix (ECM). They belong to the fibrillin/LTBP-superfamily, and are high molecular weight glycoproteins characterized by EGF-like repeats and 8-Cys repeats. Most LTBPs associate with the small latent forms of TGF-beta. Their roles include to facilitate the secretion of latent TGF-beta and to target it to the ECM. In order to identify new matrix-binding domains of LTBP-1 and to characterize their association with the extracellular matrix, we have produced (in a mammalian expression system) partly overlapping recombinant fragments of its shorter form, LTBP-1S, and analyzed the binding of the purified fusion proteins to extracellular matrices of cultured human dermal and lung fibroblasts. Recombinant fragments from three different regions of the N- and C-termini showed affinity to the matrix. These interacting regions contain either the first (hybrid), second or fourth 8-Cys domains of the LTBP-1S molecule. They bound independently to the matrix. Each of them had an ability to inhibit the association of native exogenous LTBP-1 with fibroblast extracellular matrix. The interactions of the LTBP-1 fragments with the extracellular matrix resisted treatment with sodium deoxycholate, suggesting strong, possibly covalent binding. The binding occurred in a time- and dose-dependent fashion. The N-terminal fragments bound more readily to the matrices. With all fragments the binding took place both with intact fibroblast matrices and with matrices isolated by sodium deoxycholate. When using CHO cell layers, which form sparse matrices, only the N-terminal fragment of LTBP-1 was efficiently incorporated. The association of the binding fragments with isolated matrices was enhanced by soluble, cell-derived factors. The current data suggest that LTBP-1 contains three different domains with an ability to associate with the extracellular matrix.

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Schedin, P., R. Strange, T. Mitrenga, P. Wolfe, and M. Kaeck. "Fibronectin fragments induce MMP activity in mouse mammary epithelial cells: evidence for a role in mammary tissue remodeling." Journal of Cell Science 113, no. 5 (March 1, 2000): 795–806. http://dx.doi.org/10.1242/jcs.113.5.795.

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Mammary gland form and function are regulated by interactions between epithelium and extracellular matrix. Major glycoprotein components of extracellular matrix have been identified that give survival, proliferation and differentiation signals to mammary epithelial cells. We provide evidence that proteolytic fragments of the extracellular matrix glycoprotein, fibronectin, suppress growth and can promote apoptosis of mouse mammary epithelial cells. During mammary gland involution, total fibronectin and fibronectin fragment levels are increased. The peak levels of fibronectin protein and fragments are observed 4–6 days post-weaning, coincident with the peak in epithelial cell death. Using a model for hormone withdrawal-induced death of mammary epithelium, elevated levels of fibronectin proteolytic fragments were associated with apoptosis in TM-6 cells, a tumorigenic mouse mammary epithelial cell line. Treatment of TM-6 cells with exogenous fibronectin fragments (FN120) reduced cell number, and induced apoptosis and matrix degrading protease activity. Inhibition of matrix protease activity rescued TM-6 cell viability, indicating that FN120-induced cell loss is mediated through matrix protease activity. In a three-dimensional model for mammary gland development, FN120 reduced alveolar-like and promoted ductal-like development by a matrix protease-dependent mechanism. These data suggest that during post-lactational involution, fibronectin fragments may contribute to epithelial cell loss and dissolution of mammary alveoli by inducing matrix degrading proteinases.

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Olmo, N., J. Turnay, G. Risse, R. Deutzmann, K. von der Mark, and M. A. Lizarbe. "Modulation of 5′-nucleotidase activity in plasma membranes and intact cells by the extracellular matrix proteins laminin and fibronectin." Biochemical Journal 282, no. 1 (February 15, 1992): 181–88. http://dx.doi.org/10.1042/bj2820181.

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Modulation of 5′-nucleotidase activity by the extracellular matrix proteins fibronectin, laminin and their fragments has been studied in plasma membrane preparations as well as in intact BCS-TC2 and Rugli cells. The ectoenzyme on plasma membranes is activated by laminin; fibronectin inhibits the AMPase activity on BCS-TC2 plasma membranes but no inhibitory effect is found in plasma membrane preparations from Rugli cells. These effects are dependent on the preincubation time and protein concentration. When the effect of the extracellular matrix proteins is studied on intact cells, both BCS-TC2 and Rugli cells show similar behaviour. A decrease in the enzyme activity is observed in the presence of fibronectin. The AMPase inhibitory activity is located on its 40 kDa fragment. No inhibitory activity is found in other fibronectin fragments, including the 140 kDa fragment which contains the RGDS cell-adhesion sequence. Laminin and its E1-4 and E8 fragments are able to activate the ecto-5′-nucleotidase activity of both BCS-TC2 and Rugli cells. The effect of the E1-4 fragment on intact cells is greater than that observed for the E8 fragment and uncleaved laminin. Our results suggest a bifunctional role for 5′-nucleotidase as ectoenzyme and cell receptor for extracellular matrix proteins.

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Bekaert, Sandrine, Marianne Fillet, Benoit Detry, Muriel Pichavant, Raphael Marée, Agnes Noel, Natacha Rocks, and Didier Cataldo. "Inflammation-Generated Extracellular Matrix Fragments Drive Lung Metastasis." Cancer Growth and Metastasis 10 (January 1, 2017): 117906441774553. http://dx.doi.org/10.1177/1179064417745539.

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Mechanisms explaining the propensity of a primary tumor to metastasize to a specific site still need to be unveiled, and clinical studies support a link between chronic inflammation and cancer dissemination to specific tissues. Using different mouse models, we demonstrate the role of inflammation-generated extracellular matrix fragments ac-PGP ( N-acetyl-proline-glycine-proline) on tumor cells dissemination to lung parenchyma. In mice exposed to cigarette smoke or lipopolysaccharide, lung neutrophilic inflammation produces increased levels of MMP-9 (matrix metalloproteinase 9) that contributes to collagen breakdown and allows the release of ac-PGP tripeptides. By silencing CXCR2 gene expression in tumor cells, we show that these generated ac-PGP tripeptides exert a chemotactic activity on tumor cells in vivo by binding CXCR2.

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ADAIRKIRK, T., and R. SENIOR. "Fragments of extracellular matrix as mediators of inflammation." International Journal of Biochemistry & Cell Biology 40, no. 6-7 (June 2008): 1101–10. http://dx.doi.org/10.1016/j.biocel.2007.12.005.

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7

WAGA, SHINOBU, KAZUHIKO SUGIMOTO, HIROSHI TANAKA, TATSUO ITO, TOHRU NAKAHATA, TAKASHI TATEYAMA, YOSHIKI KAKIZAKI, and MASARU YOKOYAMA. "IgA Interaction with Carboxy-Terminal 43-kD Fragment of Fibronectin in IgA Nephropathy." Journal of the American Society of Nephrology 10, no. 2 (February 1999): 256–63. http://dx.doi.org/10.1681/asn.v102256.

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Abstract. IgA deposition in the glomerular mesangial matrix is a prerequisite for the diagnosis of IgA nephropathy, and circulating IgA-containing complex has been implicated in this process. Since fibronectin is known to be involved in the assembly of extracellular matrix, this study was conducted to investigate whether fibronectin and its fragments are present in sera of patients and are capable of binding IgA1. Sera from patients with IgA nephropathy were purified by heparin-affinity chromatography, and column eluate were analyzed for the presence of fibronectin using Western blot and a set of anti-fibronectin monoclonal antibodies. Native fibronectin was digested with cathepsin D to obtain fragments similar to those of serum fibronectin. The capacity of fibronectin to bind IgA was examined with a mixture of purified IgA1 and cathepsin D-digested fibronectin fragments. A 43-kD carboxy-terminal fragment of fibronectin was detected in samples derived from sera of patients with IgA nephropathy but not in healthy control subjects. A similar-sized fragment was generated by cathepsin D digestion of the native molecule and was shown to bind to IgA1 in vitro. Since the carboxy-terminal domain is known to be critical in assembling exogenous fibronectin into the extracellular matrix, the affinity to IgA1 to a fragment found in patients may have pathogenic potential to mediate extracellular IgA deposition in IgA nephropathy.

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8

Christopher, R. A., S. R. Judge, P. A. Vincent, P. J. Higgins, and P. J. McKeown-Longo. "The amino-terminal matrix assembly domain of fibronectin stabilizes cell shape and prevents cell cycle progression." Journal of Cell Science 112, no. 19 (October 1, 1999): 3225–35. http://dx.doi.org/10.1242/jcs.112.19.3225.

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Adhesion to the extracellular matrix modulates the cellular response to growth factors and is critical for cell cycle progression. The present study was designed to address the relationship between fibronectin matrix assembly and cell shape or shape dependent cellular processes. The binding of fibronectin's amino-terminal matrix assembly domain to adherent cells represents the initial step in the assembly of exogenous fibronectin into the extracellular matrix. When added to monolayers of pulmonary artery endothelial cells, the 70 kDa fragment of fibronectin (which contains the matrix assembly domain) stabilized both the extracellular fibronectin matrix as well as the actin cytoskeleton against cytochalasin D-mediated structural reorganization. This activity appeared to require specific fibronectin sequences as fibronectin fragments containing the cell adhesion domain as well as purified vitronectin were ineffective inhibitors of cytochalasin D-induced cytoarchitectural restructuring. Such pronounced morphologic consequences associated with exposure to the 70 kDa fragment suggested that this region of the fibronectin molecule may affect specific growth traits known to be influenced by cell shape. To assess this possibility, the 70 kDa fragment was added to scrape-wounded monolayers of bovine microvessel endothelium and the effects on two shape-dependent processes (i.e. migration and proliferation) were measured as a function of time after injury and location from the wound. The addition of amino-terminal fragments of fibronectin to the monolayer significantly inhibited (by >50%) wound closure. Staining of wounded monolayers with BrdU, moreover, indicated that either the 70 kDa or 25 kDa amino-terminal fragments of fibronectin, but not the 40 kDa collagen binding fragment, also inhibited cell cycle progression. These results suggest that the binding of fibronectin's amino-terminal region to endothelial cell layers inhibits cell cycle progression by stabilizing cell shape.

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Chakraborty, Abir, Natasha Marie-Eraine Boel, and Adrienne Lesley Edkins. "HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation." Cells 9, no. 2 (January 22, 2020): 272. http://dx.doi.org/10.3390/cells9020272.

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Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly. The highest affinity interaction was with the 30-kDa (heparin-binding) FN fragment, which also showed the greatest colocalization in cells and accommodated both HSP90 and heparin in the complex. The strength of interaction with HSP90 was influenced by the inherent stability of the FN fragments, together with the type of motif, where HSP90 preferentially bound the type-I FN repeat over the type-II repeat. Exogenous extracellular HSP90 led to increased incorporation of both full-length and 70-kDa fragments of FN into fibrils. Together, our data suggested that HSP90 may regulate FN matrix assembly through its interaction with N-terminal FN fragments.

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10

Gaggar, Amit, and Nathaniel Weathington. "Bioactive extracellular matrix fragments in lung health and disease." Journal of Clinical Investigation 126, no. 9 (September 1, 2016): 3176–84. http://dx.doi.org/10.1172/jci83147.

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11

Chalikias, Georgios K., and Dimitrios N. Tziakas. "Biomarkers of the extracellular matrix and of collagen fragments." Clinica Chimica Acta 443 (March 2015): 39–47. http://dx.doi.org/10.1016/j.cca.2014.06.028.

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12

Radice, Marco, Paola Brun, Daniela Bernardi, Cristina Fontana, Roberta Cortivo, and Giovanni Abatangelo. "Clostridial Collagenase Releases Bioactive Fragments From Extracellular Matrix Molecules." Journal of Burn Care & Rehabilitation 20, no. 4 (July 1999): 282–91. http://dx.doi.org/10.1097/00004630-199907000-00003.

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13

Messent, A. J., D. S. Tuckwell, V. Knauper, M. J. Humphries, G. Murphy, and J. Gavrilovic. "Effects of collagenase-cleavage of type I collagen on alpha2beta1 integrin-mediated cell adhesion." Journal of Cell Science 111, no. 8 (April 15, 1998): 1127–35. http://dx.doi.org/10.1242/jcs.111.8.1127.

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In this paper we show that collagenase-3 cleavage of type I collagen has a marked effect on alpha2beta1 integrin-mediated interactions with the collagen fragments generated. Isolated alpha2beta1 integrin and alpha2 integrin A-domain were found to bind to both native collagen and native 3/4 fragment and, to a lesser degree, native 1/4 fragment. Whole integrin and integrin A-domain binding were lost after heat denaturation of the collagen fragments. At physiological temperature, cell adhesion to triple-helical 3/4 fragment via alpha2beta1 integrin was still possible; however, no alpha2beta1 integrin-mediated adhesion to the 1/4 fragment was observed. Unwinding of the collagen fragment triple helices by heating to physiological temperatures prior to adsorption to plastic tissue culture plates resulted in total abrogation of HT1080 cell attachment to either fragment. These results provide significant evidence in support of a role for matrix-metalloproteinase cleavage of the extracellular matrix in modifying cell-matrix interactions.

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Peters, D. M., and D. F. Mosher. "Localization of cell surface sites involved in fibronectin fibrillogenesis." Journal of Cell Biology 104, no. 1 (January 1, 1987): 121–30. http://dx.doi.org/10.1083/jcb.104.1.121.

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Fibronectin binding sites on cultured human fibroblasts were localized by high voltage electron microscopy using either 5- or 18-nm colloidal gold beads (Au5 or Au18) bound to intact fibronectin, the 70-kD amino-terminal fragment of fibronectin that blocks incorporation of exogenous fibronectin into extracellular matrix, or 160-180-kD fragments of fibronectin with cell adhesion and heparin-binding activities. Binding sites for Au18-fibronectin on the cell surface were localized to specific regions along the edge of the fibroblast and on retraction fibers. Au18-fibronectin complexes at these sites were initially localized in clusters that co-aligned with intracellular microfilament bundles. With longer incubations, Au18-fibronectin complexes were arranged into long fibrillar networks on the cell surface and in the extracellular space. The appearance of Au18-fibronectin in these fibrillar networks and disappearance of clusters of Au18-fibronectin suggest that Au18-fibronectin complexes are arranged into matrix at specific regions of the cell surface. Au18-70-kD fragment complexes initially had a similar distribution to Au18-fibronectin complexes. With longer incubations, Au18-70-kD fragment complexes were found in long linear arrangements on the cell surface. Double labeling experiments using Au18-70-kD fragment and Au5-160-180-kD fragments showed that the 70-kD fragment and the 160-180-kD fragments bind to different regions of the cell.

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Ricard-Blum, Sylvie, and Romain Salza. "Matricryptins and matrikines: biologically active fragments of the extracellular matrix." Experimental Dermatology 23, no. 7 (July 2014): 457–63. http://dx.doi.org/10.1111/exd.12435.

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Clamp, A. R., and G. C. Jayson. "The clinical potential of antiangiogenic fragments of extracellular matrix proteins." British Journal of Cancer 93, no. 9 (October 2005): 967–72. http://dx.doi.org/10.1038/sj.bjc.6602820.

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Valenzuela, Juan Carlos, Christopher Heise, Gilbert Franken, Jeet Singh, Barbara Schweitzer, Constanze I. Seidenbecher, and Renato Frischknecht. "Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1654 (October 19, 2014): 20130606. http://dx.doi.org/10.1098/rstb.2013.0606.

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Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeostatic plasticity. We hypothesized that the ECM, being rich in chondroitin sulfate proteoglycans such as brevican, which are suggested to stabilize synapses by their inhibitory effect on structural plasticity, must be remodelled to allow for structural and molecular changes during conditions of homeostatic plasticity. We found a high abundance of cleaved brevican fragments throughout the hippocampus and cortex and in neuronal cultures, with the strongest labelling in perineuronal nets on parvalbumin-positive interneurons. Using an antibody specific for a brevican fragment cleaved by the matrix metalloprotease ADAMTS4, we identified the enzyme as the main brevican-processing protease. Interestingly, we found ADAMTS4 largely associated with synapses. After inducing homeostatic plasticity in neuronal cell cultures by prolonged network inactivation, we found increased brevican processing at inhibitory as well as excitatory synapses, which is in line with the ADAMTS4 subcellular localization. Thus, the ECM is remodelled in conditions of homeostatic plasticity, which may liberate synapses to allow for a higher degree of structural plasticity.

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Bejarano, P. A., M. E. Noelken, K. Suzuki, B. G. Hudson, and H. Nagase. "Degradation of basement membranes by human matrix metalloproteinase 3 (stromelysin)." Biochemical Journal 256, no. 2 (December 1, 1988): 413–19. http://dx.doi.org/10.1042/bj2560413.

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Connective tissue cells synthesize and secrete a group of matrix metalloproteinases (MMPs), all of which are capable of degrading the extracellular-matrix components. One of them, MMP-3 (stromelysin) has been shown to degrade purified basement-membrane components, collagen IV and laminin [Okada, Y., Nagase, H. & Harris, E. D., Jr. (1986) J. Biol. Chem. 261, 14245-14255]. Here we report that MMP-3 degrades collagen IV and laminin in intact basement membranes from bovine glomeruli (GBM) and bovine anterior-lens capsules (LBM). Degradation products were analysed by SDS/polyacrylamide-gel electrophoresis to determine the number and sizes of polypeptide fragments. Immunoblotting techniques were used to identify the origins of the fragments, i.e. collagen IV or laminin. The fragments of collagen IV were further mapped using specific antibodies that recognize the N-terminal (7 S) domain, the C-terminal (NC-1) domain, or the major triple-helical region between the terminal domains. Degradation of collagen IV was extensive; many fragments were found, from both GBM and LBM, in the Mr range 25,000-380,000. A large fragment of laminin (Mr greater than 380,000) was found in the GBM digests without reduction, but it dissociated into 220,000-Mr chains upon reduction. The results suggest that MMP-3 plays an important role in the catabolism of basement membranes.

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Mongiat, Maurizio, Simone Buraschi, Eva Andreuzzi, Thomas Neill, and Renato V. Iozzo. "Extracellular matrix: the gatekeeper of tumor angiogenesis." Biochemical Society Transactions 47, no. 5 (October 11, 2019): 1543–55. http://dx.doi.org/10.1042/bst20190653.

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Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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Cheng, Aixin, Stuart A. Cain, Pinyuan Tian, Andrew K. Baldwin, Paweena Uppanan, Cay M. Kielty, and Susan J. Kimber. "Recombinant Extracellular Matrix Protein Fragments Support Human Embryonic Stem Cell Chondrogenesis." Tissue Engineering Part A 24, no. 11-12 (June 2018): 968–78. http://dx.doi.org/10.1089/ten.tea.2017.0285.

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Klotz, S. A., and R. L. Smith. "Gelatin fragments block adherence of Candida albicans to extracellular matrix proteins." Microbiology 141, no. 10 (October 1, 1995): 2681–84. http://dx.doi.org/10.1099/13500872-141-10-2681.

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Ricard-Blum, Sylvie, and Sylvain D. Vallet. "Fragments generated upon extracellular matrix remodeling: Biological regulators and potential drugs." Matrix Biology 75-76 (January 2019): 170–89. http://dx.doi.org/10.1016/j.matbio.2017.11.005.

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23

Horton, Maureen R., Mitchell A. Olman, Clare Bao, Kimberly E. White, Augustine M. K. Choi, Beek-Yok Chin, Paul W. Noble, and Charles J. Lowenstein. "Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages." American Journal of Physiology-Lung Cellular and Molecular Physiology 279, no. 4 (October 1, 2000): L707—L715. http://dx.doi.org/10.1152/ajplung.2000.279.4.l707.

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Pulmonary inflammation and fibrosis are characterized by increased turnover and production of the extracellular matrix as well as an impairment of lung fibrinolytic activity. Although fragments of the extracellular matrix component hyaluronan induce macrophage production of inflammatory mediators, the effect of hyaluronan on the fibrinolytic mediators plasminogen activator inhibitor (PAI)-1 and urokinase-type plasminogen activator (uPA) is unknown. This study demonstrates that hyaluronan fragments augment steady-state mRNA, protein, and inhibitory activity of PAI-1 as well as diminish the baseline levels of uPA mRNA and inhibit uPA activity in an alveolar macrophage cell line. Hyaluronan fragments alter macrophage expression of PAI-1 and uPA at the level of gene transcription. Similarly, hyaluronan fragments augment PAI-1 and diminish uPA mRNA levels in freshly isolated inflammatory alveolar macrophages from bleomycin-treated rats. These data suggest that hyaluronan fragments influence alveolar macrophage expression of PAI-1 and uPA and may be a mechanism for regulating fibrinolytic activity during lung inflammation.

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Penberthy, T. W., Y. Jiang, F. W. Luscinskas, and D. T. Graves. "MCP-1-stimulated monocytes preferentially utilize beta 2-integrins to migrate on laminin and fibronectin." American Journal of Physiology-Cell Physiology 269, no. 1 (July 1, 1995): C60—C68. http://dx.doi.org/10.1152/ajpcell.1995.269.1.c60.

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Recruitment of monocytes to inflammatory sites involves a series of sequential attachments and detachments to extracellular matrix proteins in response to a chemoattractant gradient. In this study we compared the migration of human peripheral blood monocytes on different extracellular matrix proteins in response to monocyte chemoattractant protein-1 (MCP-1) and N-formylmethionyl-leucyl-phenylalanine. Monocytes migrated more effectively on laminin compared with other extracellular matrix proteins. In contrast, this preference was not observed with neutrophils, suggesting that the monocytes and neutrophils may have differences in their migration on extracellular matrix proteins. To study this further, function-blocking monoclonal antibodies were used to examine mechanistically whether beta 1- and beta 2-integrins were involved in monocyte migration on fibronectin or laminin in response to MCP-1. Monocyte migration on both laminin and fibronectin was blocked 100% (P < 0.05) by intact monoclonal antibody, F(ab') fragments, and F(ab')2 fragments to beta 2-integrins. We also determined that antibodies to beta 2-integrins block monocyte migration that has already been initiated. In contrast, antibody to the beta 1-integrins inhibited monocyte migration by approximately 40% (P < 0.05). Thus monocytes that express both beta 1- and beta 2-integrins require utilization of beta 2-integrins in migration on extracellular matrix proteins. The results also suggest that beta 1-integrins facilitate monocyte migration but that monocyte migration is not absolutely dependent on the interaction of beta 1-integrins with extracellular matrix proteins. In contrast, neutrophil migration is beta 2-integrin dependent and is not facilitated by beta 1-integrins.

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Lei Ding and Danping Guo. "Extracellular Matrix Fragments as Regulators of Cartilage Metabolism in Health and Disease." Current Rheumatology Reviews 3, no. 3 (August 1, 2007): 183–96. http://dx.doi.org/10.2174/157339707781387590.

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Chernousov, M. A., M. L. Metsis, and V. E. Koteliansky. "Studies of extracellular fibronectin matrix formation with fluoresceinated fibronectin and fibronectin fragments." FEBS Letters 183, no. 2 (April 22, 1985): 365–69. http://dx.doi.org/10.1016/0014-5793(85)80811-5.

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Curtis, Patrick D., James Atwood, Ron Orlando, and Lawrence J. Shimkets. "Proteins Associated with the Myxococcus xanthus Extracellular Matrix." Journal of Bacteriology 189, no. 21 (August 31, 2007): 7634–42. http://dx.doi.org/10.1128/jb.01007-07.

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ABSTRACT Fruiting body formation of Myxococcus xanthus, like biofilm formation of many other organisms, involves the production of an extracellular matrix (ECM). While the polysaccharide component has been studied, the protein component has been largely unexplored. Proteins associated with the ECM were solubilized from purified ECM by boiling with sodium dodecyl sulfate and were identified by liquid chromatography-tandem mass spectrometry of tryptic fragments. The ECM is enriched in proteins of novel function; putative functions were assigned for only 5 of the 21 proteins. Thirteen putative ECM proteins had lipoprotein secretion signals. The genes for many ECM proteins were disrupted in the wild-type (WT), fibA, and pilA backgrounds. Disruption of the MXAN4860 gene had no effect in the WT or fibA background but in the pilA background resulted in a 24-h delay in aggregation and sporulation compared to its parent. The results of this study show that the M. xanthus ECM proteome is diverse and novel.

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Neve, Anna, Francesco Paolo Cantatore, Nicola Maruotti, Addolorata Corrado, and Domenico Ribatti. "Extracellular Matrix Modulates Angiogenesis in Physiological and Pathological Conditions." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/756078.

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Angiogenesis is a multistep process driven by a wide range of positive and negative regulatory factors. Extracellular matrix (ECM) plays a crucial role in the regulation of this process. The degradation of ECM, occurring in response to an angiogenic stimulus, leads to degradation or partial modification of matrix molecules, release of soluble factors, and exposure of cryptic sites with pro- and/or antiangiogenic activity. ECM molecules and fragments, resulting from proteolysis, can also act directly as inflammatory stimuli, and this can explain the exacerbated angiogenesis that drives and maintains several inflammatory diseases. In this review we have summarized some of the more recent literature data concerning the molecular control of ECM in angiogenesis in both physiological and pathological conditions.

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Buck, M. R., D. G. Karustis, N. A. Day, K. V. Honn, and B. F. Sloane. "Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues." Biochemical Journal 282, no. 1 (February 15, 1992): 273–78. http://dx.doi.org/10.1042/bj2820273.

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Our laboratory has previously demonstrated that increased malignancy of several histological types of human and animal tumours is associated with increases in their cathepsin B activity, particularly cathepsin B activity associated with plasma-membrane/endosomal vesicles or shed vesicles. Here we report that cathepsin B from normal or tumour tissues degrades purified extracellular-matrix components, type IV collagen, laminin and fibronectin, at both acid pH and neutral pH. The number and sizes of degradation products were analysed by SDS/PAGE. Cathepsin B from both sources exhibited similar activities towards, and similar patterns of cleavage of, the extracellular-matrix proteins. At neutral pH, cathepsin B from both sources appeared to undergo autodegradation, a process that was decreased in the presence of alternative substrates such as the extracellular-matrix proteins. Cathepsin B readily degraded type IV collagen at 25 degrees C, indicating activity towards native type IV collagen. Fibronectin degradation products of 100-200 kDa and of 18 and 22 kDa were observed. A single 70 kDa fragment was released from laminin under non-reducing conditions and multiple fragments ranging from 45 to 200 kDa under reducing conditions. These results suggest that cathepsin B at or near the surface of malignant tumour cells may play a functional role in the focal dissolution of extracellular matrices.

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Willumsen, Nicholas, Kim Leitzel, Suhail M. Ali, Vinod Nagabhairu, Eric Marks, Hyma Vani Polimera, Angelique Ellerbee Richardson, et al. "Extracellular matrix (ECM) protein fragments in serum and outcomes in two metastatic breast cancer cohorts." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 1085. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1085.

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1085 Background: Extracellular matrix (ECM) is the non-cellular component of all tissues. Increased ECM formation and matrix metallo-protease (MMP) mediated ECM degradation are parts of tumorgenesis. The altered ECM remodeling generates specific ECM fragments that are released into the circulation. We evaluated the association of specific ECM/collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. Methods: C1M (MMP-degraded type I collagen), C3M (MMP-degraded type III collagen), C4M (MMP-degraded type IV collagen), and PRO-C3 (pro-peptide reflecting truetype III collagen formation) were measured by ELISA in pre-treatment serum from a phase III randomized clinical trial of 2nd-line hormone therapy (HR+, n= 153), and a 1st-line trastuzumab-treated cohort (HER2+, n=64). In both cohorts, all sites of metastases were included. The collagen-fragments were evaluated on continuous and categorical (75th percentile cut-off) bases by univariate Cox-regression analysis for their association with time-to-progression (TTP) and overall survival (OS). Results: In the HR+ cohort, Pro-C3 measured as a continuous variable was significantly associated with TTP; C1M, C4M and Pro-C3 were associated with OS. On a categorical basis, C1M and C3M were associated with TTP; all fragments were associated with OS (Table). In the HER2+ cohort, continuous measurements of all fragments were associated with TTP and OS. On a categorical basis (Table), all fragments were associated with TTP; C4M and Pro-C3 were associated with OS. Conclusions: ECM remodeling quantified in pre-treatment serum was associated with shorter TTP and OS in two independent MBC cohorts receiving systemic therapy. If validated, quantification of ECM remodeling in serum has potential as prognostic and/or predictive biomarkers in MBC. [Table: see text]

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Boodoo, Sada, Ernst W. Spannhake, Jonathan D. Powell, and Maureen R. Horton. "Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 3 (September 2006): L479—L486. http://dx.doi.org/10.1152/ajplung.00518.2005.

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Airway epithelium is emerging as a regulator of local inflammation and immune responses. However, the cellular and molecular mechanisms responsible for the immune modulation by these cells have yet to be fully elucidated. At the cellular level, the hallmarks of airway inflammation are mucus gland hypertrophy with excess mucus production, accumulation of inflammatory mediators, inflammation in the airway walls and lumen, and breakdown and turnover of the extracellular matrix. We demonstrate that fragments of the extracellular matrix component hyaluronan induce inflammatory chemokine production in primary airway epithelial cells grown at an air-liquid interface. Furthermore, hyaluronan fragments use two distinct molecular pathways to induce IL-8 and IFN-γ-inducible protein 10 (IP-10) chemokine expression in airway epithelial cells. Hyaluronan-induced IL-8 requires the MAP kinase pathway, whereas hyaluronan-induced IP-10 utilizes the NF-κB pathway. The induction is specific to low-molecular-weight hyaluronan fragments as other glycosaminoglycans do not induce IL-8 and IP-10 in airway epithelial cells. We hypothesize that not only is the extracellular matrix a target of destruction in airway inflammation but it plays a critical role in perpetuating inflammation through the induction of cytokines, chemokines, and modulatory enzymes in epithelial cells. Furthermore, hyaluronan, by inducing IL-8 and IP-10 by distinct pathways, provides a unique target for differential regulation of key inflammatory chemokines.

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Friedlander, D. R., S. Hoffman, and G. M. Edelman. "Functional mapping of cytotactin: proteolytic fragments active in cell-substrate adhesion." Journal of Cell Biology 107, no. 6 (December 1, 1988): 2329–40. http://dx.doi.org/10.1083/jcb.107.6.2329.

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Cytotactin is an extracellular matrix glycoprotein with a restricted distribution during development. In electron microscopic images, it appears as a hexabrachion with six arms extending from a central core. Cytotactin binds to other extracellular matrix proteins including a chondroitin sulfate proteoglycan (CTB proteoglycan) and fibronectin. Although cytotactin binds to a variety of cells including fibroblasts and neurons, in some cases it causes cells in culture to round up and it inhibits their migration. To relate these various effects of cytotactin on cell behavior to its binding regions, we have examined its ability to support cell-substrate adhesion and have mapped its cell-binding function onto its structure. In a cell-substrate adhesion assay, fibroblasts bound to cytotactin but remained round. In contrast, they both attached and spread on fibronectin. Neither neurons nor glia bound to cytotactin in this assay. In an assay in which cell-substrate contact was initiated by centrifugation, however, neurons and glia bound well to cytotactin; this binding was blocked by specific anti-cytotactin antibodies. The results suggest that neurons and glia can bind to cytotactin-coated substrates and that these cells, like fibroblasts, possess cell surface ligands for cytotactin. After applying methods of limited proteolysis and fractionation, these assays were used to map the binding functions of cytotactin onto its structure. Fragments produced by limited proteolysis were fractionated into two major pools: one (fraction I) contained disulfide-linked oligomers of a 100-kD fragment and two minor related fragments, and the second (fraction II) contained monomeric 90- and 65-kD fragments. The 90- and 65-kD fragments in fraction II were closely related to each other and were structurally and immunologically distinct from the fragments in fraction I. Only components in fraction I were recognized by mAb M1, which binds to an epitope located in the proximal portion of the arms of the hexabrachion and by a polyclonal antibody prepared against a 75-kD CNBr fragment of intact cytotactin. A mAb (1D8) and a polyclonal antibody prepared against a 35-kD CNBr fragment of cytotactin only recognized components present in fraction II. In cell-binding experiments, fibroblasts, neurons, and glia each adhered to substrates coated with fraction II, but did not adhere to substrates coated with fraction I. Fab fragments of the antibody to the 35-kD CNBr fragment strongly inhibited the binding of cells to cytotactin, supporting the conclusion that fraction II contains a cell-binding region. In addition, Fab fragments of this antibody inhibited the binding of cytotactin to CTB pr

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PANDIT, Sujata G., Prasanthi GOVINDRAJ, Joachim SASSE, Peter J. NEAME, and John R. HASSELL. "The fibroblast growth factor receptor, FGFR3, forms gradients of intact and degraded protein across the growth plate of developing bovine ribs." Biochemical Journal 361, no. 2 (January 8, 2002): 231–41. http://dx.doi.org/10.1042/bj3610231.

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Point mutations in the human fibroblast growth factor (FGF) receptor 3 gene (Fgfr3) produce a constitutively active receptor, which disrupts chondrocyte differentiation in the growth plate and results in skeletal dysplasias with severe shortening of the limbs. Alternative splicing of the Fgfr3 transcript gives rise to two isoforms, IIIc and IIIb, which vary in their specificity for FGF ligands. We examined the expression of these FGFR3 isoforms in the bovine fetal rib growth plate to determine whether levels of FGFR3 expression are zone-related. Transcripts for both Fgfr3 isoforms are expressed in rib growth plate, with maximum expression in the hypertrophic region and the least expression in the reserve zone. Fgfr3 IIIc is the predominant isoform in the growth plate. Western-blot analysis revealed the presence of full-length FGFR3 (135kDa) for both isoforms in the reserve zone, a major 98kDa fragment in all zones and smaller fragments primarily in the hypertrophic zone. Immunostaining localized FGFR3 to the pericellular region of reserve chondrocytes and to the extracellular matrix in the hypertrophic zone. These results suggest that the transmembrane form of FGFR3 increasingly undergoes proteolytic cleavage towards the hypertrophic zone to produce an extracellular-domain fragment of FGFR3, which is present in large amounts in the matrix of hypertrophic cells. These findings suggest a proteolytic regulatory mechanism for FGFR3, whereby Fgfr3 fragments could control availability of FGF for the intact receptor, and by which proteolysis could inactivate the receptor.

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Kramer, R. H. "Extracellular matrix interactions with the apical surface of vascular endothelial cells." Journal of Cell Science 76, no. 1 (June 1, 1985): 1–16. http://dx.doi.org/10.1242/jcs.76.1.1.

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Cultured aortic endothelial cells, like their in vivo counterparts, form highly organized, confluent monolayers of polarized epithelioid cells that secrete, exclusively at their basal surface, an extracellular matrix to which they then attach. The influence of isolated subendothelial matrix preparations on cell polarity and monolayer organization was studied by presenting fragments of the matrix to confluent bovine aortic endothelial cell cultures. The matrix particles were immediately bound to the apical aspect of the cell monolayer and induced rapid reorganization of the monolayer into cells with a fibroblastoid morphology. To determine if fibronectin, the major glycoprotein of the subendothelial matrix, could be involved in the observed apical cell surface-matrix interactions, latex beads or small discs of Nucleopore filters were coated with the glycoprotein and presented to confluent monolayers. In a fashion similar to that observed with matrix fragments, materials coated with fibronectin caused focal reorganization of the cell layer. After contact with the coated beads, the underlying endothelial cells flowed upward and spread over the entire bead, forming a canopy of confluent cells that draped the particle. Contact of confluent monolayers with the coated filters induced similar behaviour, except that monolayer reorganization into the fibroblastoid phenotype was followed by emigration of the majority of underlying cells through the pores to the upper filter surface, where they formed a new organized cell monolayer with the typical endothelial cell morphology. Thus contact of the apical surface of endothelial cells with structures to which they adhere initiates a rapid disruption of the organized cell monolayer, followed immediately by a concerted effort of the local population to re-establish both cell polarity and monolayer contiguity. The expression of this behaviour may be important during tissue remodeling that occurs in neovascularization and during interactions with thromboemboli.

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Popova, Nadezhda V., and Manfred Jücker. "The Functional Role of Extracellular Matrix Proteins in Cancer." Cancers 14, no. 1 (January 4, 2022): 238. http://dx.doi.org/10.3390/cancers14010238.

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The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.

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Godskesen, Line, Joachim Høg Mortensen, Lone Klinge, Michael D. Jensen, Aleksander Krag, Morten A. Karsdal, Jens Kjeldsen, and Anne-Christine Bay-Jensen. "Sa1230 Specific Fragments of Extracellular Matrix Proteins Reflect Disease Activity in Ulcerative Colitis." Gastroenterology 146, no. 5 (May 2014): S—237. http://dx.doi.org/10.1016/s0016-5085(14)60834-9.

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Julian, J., R. Chiquet-Ehrismann, H. P. Erickson, and D. D. Carson. "Tenascin is induced at implantation sites in the mouse uterus and interferes with epithelial cell adhesion." Development 120, no. 3 (March 1, 1994): 661–71. http://dx.doi.org/10.1242/dev.120.3.661.

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Expression of tenascin, an extracellular matrix protein associated with morphogenetic events and altered states of cellular adhesion, was examined in mouse uterus during the peri-implantation period. A uniform low level expression of tenascin was detected in stromal extracellular matrix during the estrous cycle and days 1 through 4 of early pregnancy. During the period of blastocyst attachment (day 4.5), an intense deposition of tenascin fibrils was located in the extracellular matrix of stroma immediately subjacent to the uterine epithelium surrounding the attaching blastocyst. This localized intensity of tenascin expression was both spatially and temporally restricted. By day 5.5, differentiation of stroma in the immediate area around the embryo to form the primary decidual zone was accompanied by a reduced amount of tenascin expression in the form of fragmented fibrils. Tenascin also could be induced by an artificial stimulus in uterine stroma of mice that had been hormonally prepared for implantation. The ability of artificial stimuli to induce tenascin expression suggested that the tenascin-inducing signals were derived from uterine cells, presumably lumenal epithelium, rather than embryonic cells. Consistent with this, conditioned medium from primary cultures of uterine epithelium was found to induce tenascin expression (2- to 4-fold) in isolated uterine stroma. Artificial stimuli generated a temporal pattern of tenascin expression similar to that observed during early pregnancy; however, in the artificially induced model, tenascin was induced in stroma immediately subjacent to lumenal epithelium along the entire length of the uterus. Purified tenascin and a recombinant tenascin fragment consisting of alternatively spliced fibronectin type III repeats, interfered with maintenance of uterine epithelial cell adhesion to Matrigel. In contrast, other recombinant tenascin fragments or fibronectin had no effect in this regard. Tenascin had no effect on adhesion of uterine stroma. Collectively, these results suggest that stimulation of TN expression in stromal extracellular matrix in vivo occurs via hormonally regulated, epithelial-mesenchymal interactions and serves as an early marker for uterine receptivity and the attachment phase of implantation. Furthermore, tenascin may facilitate embryo penetration by disrupting uterine epithelial cell adhesion to underlying basal lamina.

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Sarangi, Pranita, Larry Wahl, Susana Vega, and Yoshihiko Yamada. "Fibulin-7, a member of the extracellular matrix fibulin family, regulates immune cell migration and function (P5124)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 58.16. http://dx.doi.org/10.4049/jimmunol.190.supp.58.16.

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Abstract Interactions of immune cells with matrix proteins and their bioactive fragments via integrins could influence their activation and differentiation. Fibulins are a family of secreted glycoproteins that are associated with extracellular matrices. Fibulins form intermolecular bridges within the extracellular matrix and serve as mediators for cellular processes and tissue remodeling. We previously identified the latest member of the extracellular protein fibulin family, TM14/fibulin-7, and found that fibulin-7 (Fbln7) is a cell adhesion molecule that binds to dental mesenchymes and odontoblasts. Fbln7 is also expressed in cartilage, placenta, and eyes. Because of Fbln7 expression in immunotolerant tissues, we hypothesized that Fbln7 or its fragment may function as an immunomodulator. In this report, we examined the effect of the full-length Fbln7-d2 and its C-terminal fragment Fbln7-d3 on immune cell functions using human monocytes. We showed that monocytes interacted with both Fbln7-d2 and -d3 in part through integrins α5β1 and α2β1. We found that Fbln7-d3 inhibited cell spreading and stress fiber formation and blocked the production of inflammatory cytokine IL-6 and MMP-1/9, while Fbln7-d2 reduced production of IL-6 and also promoted the production of IL-10. Fbln7-d3 reduced phosphorylation of Erk1/2 in TNFα-activated monocytes in vitro. Our results suggest that both full length Fbln7-d2 and Fbln7-d3 fragment are negative regulators of inflammation with distinct effects.

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Bonasia, Davide Edoardo, James A. Martin, Antongiulio Marmotti, Richard L. Amendola, Joseph A. Buckwalter, Roberto Rossi, Davide Blonna, Huston Davis Adkisson, and Annunziato Amendola. "Cocultures of Adult and Juvenile Chondrocytes Compared With Adult and Juvenile Chondral Fragments." American Journal of Sports Medicine 39, no. 11 (August 9, 2011): 2355–61. http://dx.doi.org/10.1177/0363546511417172.

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Background: The use of allogenic juvenile chondrocytes or autologous chondral fragments has shown promising laboratory results for the repair of chondral lesions. Hypothesis: Juvenile chondrocytes would not affect matrix production when mixed with adult chondrocytes or cartilage fragments. Study Design: Controlled laboratory study. Methods: Cartilage sources consisted of 3 adult and 3 juvenile (human) donors. In part 1, per each donor, juvenile chondrocytes were mixed with adult chondrocytes in 5 different proportions: 100%, 50%, 25%, 12.5%, and 0%. Three-dimensional cultures in low-melt agarose were performed. At 6 weeks, biochemical and histologic analyses were performed. In part 2, isolated adult, isolated juvenile, and mixed 3-dimensional cultures (1:1) were performed with chondral fragments (<1 mm), both with low-melt agarose and a hyaluronic acid scaffold. At 2 and 6 weeks, cultures were evaluated with biochemical and histologic analyses. Results: Part 1: Biochemical and histologic analyses showed that isolated juvenile cultures performed significantly better than mixed and isolated adult cultures. No significant differences were noted between mixed cultures (1:1) and isolated adult cultures. Part 2: Biochemical and histologic results at 6 weeks showed that mixed cartilage fragment cultures performed better than isolated adult cultures in terms of proteoglycans/DNA ratio ( P = .014), percentage of safranin O–positive cells ( P = .012), Bern score ( P = .001), and collagen type II. No statistically significant difference was noted between juvenile and mixed cultures. Conclusion: Extracellular matrix production of juvenile chondrocytes is inhibited by adult chondrocytes. The addition of juvenile cartilage fragments to adult fragments improves matrix production, with a positive interaction between the 2 sources. Clinical Relevance: Even if the underlying mechanisms are still unknown, this study describes the behavior of juvenile/adult cocultures using both chondrocytes and cartilage fragments, with potential for new research and clinical applications.

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Horton, Maureen R., Steven Shapiro, Clare Bao, Charles J. Lowenstein, and Paul W. Noble. "Induction and Regulation of Macrophage Metalloelastase by Hyaluronan Fragments in Mouse Macrophages." Journal of Immunology 162, no. 7 (April 1, 1999): 4171–76. http://dx.doi.org/10.4049/jimmunol.162.7.4171.

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Abstract Although the metalloproteinase murine metalloelastase (MME) has been implicated in lung disorders such as emphysema and pulmonary fibrosis, the mechanisms regulating MME expression are unclear. Low m.w. fragments of the extracellular matrix component hyaluronan (HA) that accumulate at sites of lung inflammation are capable of inducing inflammatory gene expression in macrophages (Mφ). The purpose of this study was to examine the effect of HA fragments on the expression of MME in alveolar Mφ. The mouse alveolar Mφ cell line MH-S was stimulated with HA fragments over time, total RNA was isolated, and Northern blot analysis was performed. HA fragments induced MME mRNA in a time-dependent fashion, with maximal levels at 6 h. HA fragments also induced MME protein expression as well as enzyme activity. The induction of MME gene expression was specific for low m.w. HA fragments and dependent upon new protein synthesis; it occurred at the level of gene transcription. We also examined the effect of HA fragments on MME expression in inflammatory alveolar Mφ from bleomycin-injured rat lungs. Although normal rat alveolar Mφ did not express MME mRNA in response to HA fragments, alveolar Mφ from the bleomycin-treated rats responded to HA fragment stimulation by increasing MME mRNA levels. Furthermore, baseline and HA fragment-induced MME gene expression in alveolar Mφ from bleomycin-treated rats was inhibited by IFN-γ. These data suggest that HA fragments may be an important mechanism for the expression of MME by Mφ in inflammatory lung disorders.

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Stupack, Dwayne G., Erguang Li, Steve A. Silletti, Jacqueline A. Kehler, Robert L. Geahlen, Klaus Hahn, Glen R. Nemerow, and David A. Cheresh. "Matrix Valency Regulates Integrin-mediated Lymphoid Adhesion via Syk Kinase." Journal of Cell Biology 144, no. 4 (February 22, 1999): 777–88. http://dx.doi.org/10.1083/jcb.144.4.777.

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Lymphocytes accumulate within the extracellular matrix (ECM) of tumor, wound, or inflammatory tissues. These tissues are largely comprised of polymerized adhesion proteins such as fibrin and fibronectin or their fragments. Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation. This adhesion event depends on the appropriate spacing of integrin adhesion sites. Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes. In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments. These results reveal a cooperative interaction between signals emanating from integrins and antigen receptors that can serve to regulate stable lymphoid cell adhesion and retention within a remodeling ECM.

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Walker, P. D., G. P. Kaushal, and S. V. Shah. "Presence of a distinct extracellular matrix-degrading metalloproteinase activity in renal tubules." Journal of the American Society of Nephrology 5, no. 1 (July 1994): 55–61. http://dx.doi.org/10.1681/asn.v5155.

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Renal tubular homogenates incubated with [3H]laminin (2 micrograms, 10(5) cpm) at 37 degrees C resulted in time- and protein-dependent laminin degradation (e.g., at 24 h, control = 6,533 +/- 771; experimental = 27,610 +/- 1,023 cpm +/- SE; N = 20). Gel chromatography confirmed that laminin (800 to 900 kd) was degraded to 20- to 50-kd fragments. Laminin degradation was not significantly decreased by serine or cysteine protease inhibitors. In contrast, metal chelators produced marked inhibition (EDTA, 93 +/- 3%; 1,10-phenanthroline, 99 +/- 1%) indicating that, at neutral pH, metalloproteinases were responsible for the laminin degradation. Laminin-degrading activity in renal tubules was not inhibited by the tissue inhibitor of metalloproteinase and was present in an active form. This activity was also present in high concentrations in the renal cortex and medulla but was only minimal in the liver. Further studies of the renal cortex revealed a similar metalloproteinase activity against type IV collagen (11,075 +/- 305; N = 6) and gelatin (41,026 +/- 1,373; N = 6), and this activity was membrane associated (97 +/- 1%; N = 4). Taken together, the characteristics of this renal metalloproteinase indicate that it is distinct from classic matrix-degrading metalloproteinases. The release of this distinct metalloproteinase from damaged renal tubular epithelial cells during injury may result in the production of fragments of laminin or other extracellular matrix components with biologic effects relevant to renal regeneration.

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Xie, DL, R. Meyers, and GA Homandberg. "Release of elastase from monocytes adherent to a fibronectin-gelatin surface." Blood 81, no. 1 (January 1, 1993): 186–92. http://dx.doi.org/10.1182/blood.v81.1.186.186.

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Abstract Fibronectin (Fn) is a circulating and extracellular matrix glycoprotein that may serve to facilitate phagocytosis because of its ability to bind many inflammatory ligands and to a monocyte receptor. Fn fragments have been shown in many systems to have augmented properties over those of native Fn. We show in this report that although Fn fragments did not cause elastase release from monocytes in suspension, fragments did cause elastase release from monocytes that were first bound to Fn- gelatin surfaces. An amino-terminal 29-Kd and a 140-Kd integrin-binding fragment were half-maximally active at 100 nmol/L, whereas the Arg-Gly- Asp-Ser integrin-recognition peptide was half-maximally active at 100 mumol/L. Fluid-phase Fn was ineffective yet blocked the activity of the Fn fragments. Complexing of Fn with gelatin or with heparin partially removed the blocking effect of Fn. Similar results were obtained with U- 937 cells. Substitution of the Fn-gelatin surface with bovine articular cartilage also promoted elastase release. Therefore, in conditions in vivo in which monocytes bind to tissue surface, a high ratio of Fn fragments to native Fn may upregulate certain monocyte activities such as protease release.

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Xie, DL, R. Meyers, and GA Homandberg. "Release of elastase from monocytes adherent to a fibronectin-gelatin surface." Blood 81, no. 1 (January 1, 1993): 186–92. http://dx.doi.org/10.1182/blood.v81.1.186.bloodjournal811186.

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Fibronectin (Fn) is a circulating and extracellular matrix glycoprotein that may serve to facilitate phagocytosis because of its ability to bind many inflammatory ligands and to a monocyte receptor. Fn fragments have been shown in many systems to have augmented properties over those of native Fn. We show in this report that although Fn fragments did not cause elastase release from monocytes in suspension, fragments did cause elastase release from monocytes that were first bound to Fn- gelatin surfaces. An amino-terminal 29-Kd and a 140-Kd integrin-binding fragment were half-maximally active at 100 nmol/L, whereas the Arg-Gly- Asp-Ser integrin-recognition peptide was half-maximally active at 100 mumol/L. Fluid-phase Fn was ineffective yet blocked the activity of the Fn fragments. Complexing of Fn with gelatin or with heparin partially removed the blocking effect of Fn. Similar results were obtained with U- 937 cells. Substitution of the Fn-gelatin surface with bovine articular cartilage also promoted elastase release. Therefore, in conditions in vivo in which monocytes bind to tissue surface, a high ratio of Fn fragments to native Fn may upregulate certain monocyte activities such as protease release.

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Derkacz, Alicja, Paweł Olczyk, Krystyna Olczyk, and Katarzyna Komosinska-Vassev. "The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases." Journal of Clinical Medicine 10, no. 5 (March 8, 2021): 1122. http://dx.doi.org/10.3390/jcm10051122.

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The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD). The increased activity of proteases, especially matrix metalloproteinases (MMPs), leads to excessive degradation of the extracellular matrix and the release of protein and glycoprotein fragments, previously joined with the extracellular matrix, into the circulation. MMPs participate in regulating the functions of the epithelial barrier, the immunological response, and the process of wound healing or intestinal fibrosis. At a later stage of fibrosis during IBD, excessive formation and deposition of the matrix is observed. To assess changes in the extracellular matrix, quantitative measurement of the concentration in the blood of markers dependent on the activity of proteases, involved in the breakdown of extracellular matrix proteins as well as markers indicating the formation of a new ECM, has recently been proposed. This paper describes attempts to use the quantification of ECM components as markers to predict intestinal fibrosis and evaluate the healing process of the gut. The markers which reflect increased ECM degradation, together with the ones which show the process of creating a new matrix during IBD, allow the attainment of important information regarding the changes in the intestinal tissue, epithelial integrity and extracellular matrix remodeling. This paper contains evidence confirming that ECM remodeling is an integral part of directional cell signaling in the progression of IBD, and not only a basis for the ongoing processes.

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Ryniers, Filip, Christophe Stove, Marc Goethals, Liesbeth Brackenier, Veerle Noë, Marc Bracke, Joël Vandekerckhove, Marc Mareel, and Erik Bruyneel. "Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion." Biological Chemistry 383, no. 1 (January 23, 2002): 159–65. http://dx.doi.org/10.1515/bc.2002.016.

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Abstract Matrix metalloproteases from the cell surface cleave an 80 kDa Ecadherin fragment (sECAD) that induces invasion of cancer cells into collagen type I and inhibits cellular aggregation. Conditioned media from MDCKts.srcCl2 cells at 40 C and 35 C, PCm.src5 and COLO-16 cells at 37 C contained spontaneously released sECAD; these 48 h old conditioned media were capable of inhibiting Ecadherin functions in a paracrine way. Here we show direct cleavage of the extracellular domain of Ecadherin by the serine protease plasmin. sECAD released by plasmin inhibits Ecadherin functions as evidenced by induction of invasion into collagen type I and inhibition of cellular aggregation. This functional inhibition by sECAD was reversed by aprotinin or by immunoadsorption on protein Sepharose 4 fast flow beads with antibodies against the extracellular part of Ecadherin. Our results demonstrate that plasmin produces extracellular Ecadherin fragments which regulate Ecadherin function in cells containing an intact Ecadherin/ catenin complex.

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Virkola, Ritva, Mirko Brummer, Heikki Rauvala, Loek van Alphen, and Timo K. Korhonen. "Interaction of Fimbriae of Haemophilus influenzae Type B with Heparin-Binding Extracellular Matrix Proteins." Infection and Immunity 68, no. 10 (October 1, 2000): 5696–701. http://dx.doi.org/10.1128/iai.68.10.5696-5701.2000.

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ABSTRACT The interaction of the fimbriae of Haemophilus influenzae type b (Hib) with two heparin-binding extracellular matrix proteins, human fibronectin (Fn) and heparin-binding growth-associated molecule (HB-GAM) from mouse, were studied. The fimbriated Hib strain 770235 fim+, as well as the recombinant strainE. coli HB101(pMH140), which expressed Hib fimbriae, adhered strongly to Fn and HB-GAM immobilized on glass. Purified Hib fimbriae bound to Fn and HB-GAM, and within the Fn molecule, the binding was localized to the N-terminal 30,000-molecular-weight (30K) and 40K fragments, which contain heparin-binding domains I and II, respectively. Fimbrial binding to Fn, HB-GAM, and the 30K and the 40K fragments was inhibited by high concentrations of heparin. The results show that fimbriae of Hib interact with heparin-binding extracellular matrix proteins. The nonfimbriated Hib strain 770235 fim− exhibited a low level of adherence to Fn but did not react with HB-GAM, indicating that Hib strains also possess a fimbria-independent mechanism to interact with Fn.

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Schwartz, E., S. Goldfischer, B. Coltoff-Schiller, and O. O. Blumenfeld. "Extracellular matrix microfibrils are composed of core proteins coated with fibronectin." Journal of Histochemistry & Cytochemistry 33, no. 4 (April 1985): 268–74. http://dx.doi.org/10.1177/33.4.3980980.

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Extracellular proteins of cultured calf aortic smooth muscle cells consist predominantly of microfibrils 10-20 nm in diameter typical of "elastin-associated" microfibrils described in many tissues. Chemical and immunochemical evidence is presented that microfibrils consist of at least two proteins: core protein and fibronectin. Insoluble proteins of the microfibrils were obtained in the form of a pellet and antibodies raised in rabbits against these components. The antisera reacted with the insoluble microfibrillar proteins and with soluble fibronectin in enzyme-linked immunosorbent assay, and immunostained the extracellular microfibrils in cultured cells. An immunoglobulin (Ig) fraction was prepared and absorbed with fibronectin. The absorbed IgG retained its reactivity with the microfibrillar proteins but was no longer reactive with soluble fibronectin. Immunofluorescence studies were carried out using the absorbed IgG and IgG to soluble fibronectin. Both antibodies showed immunoreactive microfibrils in the extracellular matrix of cells in log phase. However, with increasing time in culture, as the cells reached confluence, the immunofluorescence of microfibrils reacting with the absorbed IgG became less intense, whereas that of microfibrils reacting with IgG to fibronectin increased; in confluent cells, essentially no staining was detected with the absorbed IgG, and a dense network of intensely stained microfibrils was seen with IgG to fibronectin. Treatment of these cultures with urea led to partial dissociation of the fibronectin and increased visualization of the microfibrils with the absorbed IgG; double-label immunofluorescence showed that both proteins occurred on the same microfibrils. The localization of immunoreactive sites to the extracellular microfibrils was confirmed by immunoelectron microscopy. Nearly quantitative cleavage with CNBr failed to dissociate the antigenically active fragments of fibronectin from the CNBr fragments of the core proteins of the microfibrils. It was concluded that microfibrils contain core proteins and fibronectin that are codistributed in insoluble, possibly covalently cross-linked, aggregates. The core proteins are first deposited by the cell and, as a function of time in culture, fibronectin gradually coats their surface.

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Jones, P. L., N. Boudreau, C. A. Myers, H. P. Erickson, and M. J. Bissell. "Tenascin-C inhibits extracellular matrix-dependent gene expression in mammary epithelial cells. Localization of active regions using recombinant tenascin fragments." Journal of Cell Science 108, no. 2 (February 1, 1995): 519–27. http://dx.doi.org/10.1242/jcs.108.2.519.

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The physiological role of tenascin in vivo has remained obscure. Although tenascin is regulated in a stage and tissue-dependent manner, knock-out mice appear normal. When tenascin expression was examined in the normal adult mouse mammary gland, little or none was present during lactation, when epithelial cells actively synthesize and secrete milk proteins in an extracellular matrix/lactogenic hormone-dependent manner. In contrast, tenascin was prominently expressed during involution, a stage characterized by the degradation of the extracellular matrix and the subsequent loss of milk production. Studies with mammary cell lines indicated that tenascin expression was high on plastic, but was suppressed in the presence of the laminin-rich, Engelbreth-Holm-Swarm (EHS) tumour biomatrix. When exogenous tenascin was added together with EHS to mammary epithelial cells, beta-casein protein synthesis and steady-state mRNA levels were inhibited in a concentration-dependent manner. Moreover, this inhibition by tenascin could be segregated from its effects on cell morphology. Using two beta-casein promoter constructs attached to the chloramphenicol acetyltransferase reporter gene we showed that tenascin selectively suppressed extracellular matrix/prolactin-dependent transcription of the beta-casein gene in three-dimensional cultures. Finally, we mapped the active regions within the fibronectin type III repeat region of the tenascin molecule that are capable of inhibiting beta-casein protein synthesis. Our data are consistent with a model where both the loss of a laminin-rich basement membrane by extracellular matrix-degrading enzymes and the induction of tenascin contribute to the loss of tissue-specific gene expression and thus the involuting process.

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Nargis, Nurun N., Ralph C. Aldredge, and Robert D. Guy. "The influence of soluble fragments of extracellular matrix (ECM) on tumor growth and morphology." Mathematical Biosciences 296 (February 2018): 1–16. http://dx.doi.org/10.1016/j.mbs.2017.11.014.

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Journal articles on the topic 'Extracellular matrix fragments'

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