The binding of heparin to the extracellular matrix of endothelial cells up-regulates the synthesis of an antithrombotic heparan sulfate proteoglycan

2008 ◽  
Vol 217 (2) ◽  
pp. 328-337 ◽  
Author(s):  
Edvaldo S. Trindade ◽  
Constance Oliver ◽  
Maria C. Jamur ◽  
Hugo A.O. Rocha ◽  
Célia R.C. Franco ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan

scholarly journals Characterization of a novel heparan sulfate proteoglycan found in the extracellular matrix of liver sinusoids and basement membranes.

1991 ◽  
Vol 113 (5) ◽  
pp. 1231-1241 ◽  
Author(s):  
C J Soroka ◽  
M G Farquhar
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Heparan Sulfate ◽  
Rat Liver ◽  
Core Protein ◽  
Heparan Sulfate Proteoglycan ◽  
Basement Membranes ◽  
Sulfate Proteoglycan ◽  
Sinusoidal Cell ◽  
Space Of Disse

A novel heparan sulfate proteoglycan (HSPG) present in the extracellular matrix of rat liver has been partially characterized. Proteoglycans were purified from a high salt extract of total microsomes from rat liver and found to consist predominantly (approximately 90%) of HSPG. A polyclonal antiserum raised against this fraction specifically recognized HSPG by immunoprecipitation and immunoblotting. The intact, fully glycosylated HSPG migrated as a broad smear (150-300 kD) by SDS-PAGE, but after deglycosylation with trifluoromethanesulfonic acid only a single approximately 40-kD band was seen. By immunocytochemistry this HSPG was localized in the perisinusoidal space of Disse associated with irregular clumps of basement membrane-like extracellular matrix material, some of which was closely associated with the hepatocyte sinusoidal cell surface. It was also localized in biosynthetic compartments (rough ER and Golgi cisternae) of hepatocytes, suggesting that this HSPG is synthesized and deposited in the space of Disse by the hepatocyte. The anti-liver HSPG IgG also stained basement membranes of hepatic blood vessels and bile ducts as well as those of kidney and several other organs (heart, pancreas, and intestine). An antibody that recognizes the basement membrane HSPG found in the rat glomerular basement membrane did not precipitate the 150-300-kD rat liver HSPG. We conclude that the liver sinusoidal space of Disse contains a novel population of HSPG that differs in its overall size, its distribution and in the size of its core protein from other HSPG (i.e., membrane-intercalated HSPG) previously described in rat liver. It also differs in its core protein size from HSPG purified from other extracellular matrix sources. This population of HSPG appears to be a member of the basement membrane HSPG family.

Antiangiogenic antithrombin down-regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan, in endothelial cells

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1185-1191 ◽  
Author(s):  
Weiqing Zhang ◽  
Yung-Jen Chuang ◽  
Richard Swanson ◽  
Juan Li ◽  
Kyunga Seo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Transforming Growth Factor ◽  
Limited Proteolysis ◽  
Heparan Sulfate Proteoglycan ◽  
Endothelial Cell Proliferation ◽  
Cycle Phase ◽  
Sulfate Proteoglycan ◽  
Down Regulation

Abstract Antithrombin, a key serpin family regulator of blood coagulation proteases, is transformed into a potent antiangiogenic factor by limited proteolysis or mild heating. Here, we show by cDNA microarray, semiquantitative reverse transcriptase–polymerase chain reaction (RT-PCR), Northern blotting, and immunoblotting analyses that the expression of the proangiogenic heparan sulfate proteoglycan (HSPG), perlecan, but not other HSPGs, is dramatically down-regulated in human umbilical vein endothelial cells (HUVECs) treated with antiangiogenic cleaved and latent forms of antithrombin but not with the native form. Down-regulation of perlecan expression by cleaved and latent antithrombins was observed in both basic fibroblast growth factor (bFGF)–stimulated and unstimulated cells, whereas the antiangiogenic antithrombins inhibited the proliferation of only bFGF-stimulated HUVECs by arresting cells at the G1 cell cycle phase. The importance of perlecan expression levels in mediating the antiproliferative effect of the antiangiogenic antithrombins was suggested by the finding that transforming growth factor-β1, a potent stimulator of perlecan expression in endothelial cells, blocked the down-regulation of perlecan expression and antiproliferative activity of cleaved antithrombin on endothelial cells. The previously established key role of perlecan in mediating bFGF stimulation of endothelial cell proliferation and angiogenesis suggests that a primary mechanism by which antiangiogenic antithrombins exert their effects is through the down-regulation of perlecan expression.

scholarly journals Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin triggering and its mediated adhesion to endothelial cells.

1996 ◽  
Vol 184 (5) ◽  
pp. 1987-1997 ◽  
Author(s):  
Y Tanaka ◽  
K Kimata ◽  
A Wake ◽  
S Mine ◽  
I Morimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycan ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Proteoglycan Synthesis ◽  
Sulfate Proteoglycan ◽  
Heparin Binding

Leukocyte migration from circulation into tissue depends on leukocyte integrin-mediated adhesion to endothelium, but integrins cannot function until activated. However, it remains to be understood how tumor cells adhere to endothelium and infiltrate into underlying tissue. We studied mechanisms of extravasation of leukemic cells using adult T cell leukemia (ATL) cells and report the following novel features of cell surface heparan sulfate proteoglycan on ATL cells in ATL cell adhesion to endothelium: ATL cells adhere to endothelial cells through already activated integrins without exogenous stimulation; different from any other hematopoietic cells, ATL cells express a characteristic heparan sulfate capable of immobilizing heparin-binding chemokine macrophage inflammatory protein (MIP)-1 beta, a potent T cell integrin trigger, produced by the cells themselves; competitive interruption of endogenous heparan sulfate proteoglycan synthesis reduces cell surface MIP-1 beta and prevents ATL cells from integrin-mediated adhesion to endothelial cells or intercellular adhesion molecule-1 triggered through G-protein. We propose that leukemic cells adhere to endothelial cells through the adhesion cascade, similar to normal leukocyte, and that the cell surface heparan sulfate, particularly on ATL cells, is pivotally involved in chemokine-dependent autocrine stimulation of integrin triggering by immobilizing the chemokine on them.

scholarly journals Matrix-associated heparan sulfate proteoglycan: core protein-specific monoclonal antibodies decorate the pericellular matrix of connective tissue cells and the stromal side of basement membranes.

1989 ◽  
Vol 109 (6) ◽  
pp. 3199-3211 ◽  
Author(s):  
A Heremans ◽  
B van der Schueren ◽  
B de Cock ◽  
M Paulsson ◽  
J J Cassiman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Monoclonal Antibodies ◽  
Epithelial Cell ◽  
Heparan Sulfate ◽  
Core Protein ◽  
Structural Features ◽  
Heparan Sulfate Proteoglycan ◽  
Basement Membranes ◽  
Lung Fibroblasts ◽  
Sulfate Proteoglycan

Cultured human lung fibroblasts produce a large, nonhydrophobic heparan sulfate proteoglycan that accumulates in the extracellular matrix of the monolayer (Heremans, A., J. J. Cassiman, H. Van den Berghe, and G. David. 1988. J. Biol. Chem. 263: 4731-4739). A panel of four monoclonal antibodies, specific for four distinct epitopes on the 400-kD core protein of this extracellular matrix heparan sulfate proteoglycan, detects similar proteoglycans in human epithelial cell cultures. Immunohistochemistry of human tissues with the monoclonal antibodies reveals that these proteoglycans are concentrated at cell-matrix interfaces. Immunogold labeling of ultracryosections of human skin indicates that the proteoglycan epitopes are nonhomogeneously distributed over the width of the basement membrane. Immunochemical investigations and amino acid sequence analysis indicate that the proteoglycan from the fibroblast matrix shares several structural features with the large, low density heparan sulfate proteoglycan isolated from the Engelbreth-Holm-Swarm sarcoma. Thus, both epithelial cell sheets and individual mesenchymal cells accumulate a large heparan sulfate proteoglycan(s) at the interface with the interstitial matrix, where the proteoglycan may adopt a specific topological orientation with respect to this matrix.

scholarly journals Immunoelectron microscopy of endothelial cells in rat incisor suggests that most basement membrane components are produced by young cells, whereas heparan sulfate proteoglycan is produced by both young and old cells.

1988 ◽  
Vol 36 (7) ◽  
pp. 763-773 ◽  
Author(s):  
I C Murray ◽  
C P Leblond
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Heparan Sulfate ◽  
Collagen Iv ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Incisor Tooth ◽  
Rat Incisor ◽  
Membrane Components ◽  
Basement Membrane Components

When periodontal capillaries of rat incisor tooth were immunostained for four basement membrane components (laminin, collagen IV, fibronectin, heparan sulfate proteoglycan), all four were detected in the secretory organelles of endothelial cells located within 3 mm of the tooth's proximal end, but only the proteoglycan was observed in cells located 4 mm away and beyond (Experiment I). [3H]-Thymidine autoradiography revealed that the endothelial cells located at the tooth's proximal end were young and actively dividing, whereas those located 4 mm or more away were older and generally quiescent (Experiment II). Since immunostaining of a cell's secretory organelles for a given substance indicates production of this substance, the first experiment shows that endothelial cells at the proximal end produce the four basement membrane components. The second experiment discloses that these cells are young. As for the endothelial cells located 4 mm or more beyond the proximal end, the first experiment reveals that they produce only heparan sulfate proteoglycan, while the second shows that they are relatively old. Production of laminin, collagen IV, and fibronectin only by young cells implies that these substances are long-lived and stable components of basement membrane, whereas production of the proteoglycan by both young and old cells implies that it is labile and continually replaced.

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