Structure of low density heparan sulfate proteoglycan isolated from a mouse tumor basement membrane

The Engelbreth-Holm-Swarm mouse tumor has been found to produce at least two molecular species of heparan sulfate proteoglycan, a low density one (LD) and a high density one, which differ not only in core proteins but also in glycosaminoglycan structures (Kato, M., Y. Koike, Y. Ito, S. Suzuki, and K. Kimata. 1987. J. Biol. Chem. 262:7180-7188). With aim at investigating their distribution and possible functions in tissues, monoclonal antibodies were produced. Hybridomas obtained by fusion of NS-1 mouse myeloma cells with spleen cells from the rat immunized with a mixture of these proteoglycans were selected by their ability to react with the antigen. Two of them secreted monoclonal antibodies (IgG2a), designated HK-84 and HK-102, that recognize specifically the core protein moiety of LD. Immunofluorescent staining of various tissues (skeletal muscle, cardiac muscle, lung, brain, and kidney) with these monoclonal antibodies has demonstrated that the antigen molecules were present in all basement membranes of these tissues. SDS-PAGE of heparitinase-treated proteoglycan fractions prepared from these tissues and subsequent immunoblotting using these monoclonal antibodies have confirmed that the antigen molecule was LD, and further suggested that there was a tissue-specific variation in the core molecular size. Based on these results, we propose that LD may be an essential component in all basement membranes.

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High concentrations of low density lipoprotein decrease basement membrane-associated heparan sulfate proteoglycan in cultured endothelial cells

FEBS Letters ◽

10.1016/0014-5793(90)80758-b ◽

1990 ◽

Vol 264 (1) ◽

pp. 37-39 ◽

Cited By ~ 14

Author(s):

Bernhard Olgemöller ◽

Erwin D. Schleicher ◽

Susanne Schwaabe ◽

Hans-Joachim Guretzki ◽

Klaus D. Gerbitz

Keyword(s):

Endothelial Cells ◽

Basement Membrane ◽

Heparan Sulfate ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Heparan Sulfate Proteoglycan ◽

Low Density ◽

Sulfate Proteoglycan ◽

Cultured Endothelial Cells ◽

High Concentrations

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High resolution immunoelectron microscopic localization of functional domains of laminin, nidogen, and heparan sulfate proteoglycan in epithelial basement membrane of mouse cornea reveals different topological orientations.

The Journal of Cell Biology ◽

10.1083/jcb.107.4.1599 ◽

1988 ◽

Vol 107 (4) ◽

pp. 1599-1610 ◽

Cited By ~ 99

Author(s):

J C Schittny ◽

R Timpl ◽

J Engel

Keyword(s):

Basement Membrane ◽

Heparan Sulfate ◽

Heparan Sulfate Proteoglycan ◽

Low Density ◽

Sulfate Proteoglycan ◽

Lamina Densa ◽

Epithelial Basement Membrane ◽

Domain 3 ◽

Epithelial Basement ◽

Domain 4

Thin and ultrathin cryosections of mouse cornea were labeled with affinity-purified antibodies directed against either laminin, its central segments (domain 1), the end of its long arm (domain 3), the end of one of its short arms (domain 4), nidogen, or low density heparan sulfate proteoglycan. All basement membrane proteins are detected by indirect immunofluorescence exclusively in the epithelial basement membrane, in Descemet's membrane, and in small amorphous plaques located in the stroma. Immunoelectron microscopy using the protein A-gold technique demonstrated laminin domain 1 and nidogen in a narrow segment of the lamina densa at the junction to the lamina lucida within the epithelial basement membrane. Domain 3 shows three preferred locations at both the cellular and stromal boundaries of the epithelial basement membrane and in its center. Domain 4 is located predominantly in the lamina lucida and the adjacent half of the lamina densa. The low density heparan sulfate proteoglycan is found all across the basement membrane showing a similar uniform distribution as with antibodies against the whole laminin molecule. In Descemet's membrane an even distribution was found with all these antibodies. It is concluded that within the epithelial basement membrane the center of the laminin molecule is located near the lamina densa/lamina lucida junction and that its long arm favors three major orientations. One is close to the cell surface indicating binding to a cell receptor, while the other two are directed to internal matrix structures. The apparent codistribution of laminin domain 1 and nidogen agrees with biochemical evidence that nidogen binds to this domain.

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Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues: a possible pathogenesis of cholesterol granulomas in jaw cysts

Journal of Oral Pathology and Medicine ◽

10.1111/j.0904-2512.2004.00087.x ◽

2004 ◽

Vol 33 (3) ◽

pp. 177-184 ◽

Cited By ~ 26

Author(s):

Manabu Yamazaki ◽

Jun Cheng ◽

Natsuko Hao ◽

Ritsuo Takagi ◽

Shiro Jimi ◽

...

Keyword(s):

Basement Membrane ◽

Heparan Sulfate ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Heparan Sulfate Proteoglycan ◽

Low Density ◽

Sulfate Proteoglycan ◽

Jaw Cysts ◽

Membrane Type

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Origin and deposition of basement membrane heparan sulfate proteoglycan in the developing intestine.

The Journal of Cell Biology ◽

10.1083/jcb.109.4.1837 ◽

1989 ◽

Vol 109 (4) ◽

pp. 1837-1848 ◽

Cited By ~ 59

Author(s):

P Simon-Assmann ◽

F Bouziges ◽

M Vigny ◽

M Kedinger

Keyword(s):

Basement Membrane ◽

Heparan Sulfate ◽

Developmental Stages ◽

Heparan Sulfate Proteoglycan ◽

Basement Membranes ◽

Immunofluorescent Staining ◽

Rat Tissues ◽

Mouse Tumor ◽

Sulfate Proteoglycan ◽

Adult Mice

The deposition of intestinal heparan sulfate proteoglycan (HSPG) at the epithelial-mesenchymal interface and its cellular source have been studied by immunocytochemistry at various developmental stages and in rat/chick interspecies hybrid intestines. Polyclonal heparan sulfate antibodies were produced by immunizing rabbits with HSPG purified from the Engelbreth-Holm-Swarm mouse tumor; these antibodies stained rat intestinal basement membranes. A monoclonal antibody (mAb 4C1) produced against lens capsule of 11-d-old chick embryo reacted with embryonic or adult chick basement membranes, but did not stain that of rat tissues. Immunoprecipitation experiments indicated that mAb 4C1 recognized the chicken basement membrane HSPG. Immunofluorescent staining with these antibodies allowed us to demonstrate that distribution of HSPG at the epithelial-mesenchymal interface varied with the stages of intestinal development, suggesting that remodeling of this proteoglycan is essential for regulating cell behavior during morphogenesis. The immunofluorescence pattern obtained with the two species-specific HSPG antibodies in rat/chick epithelial/mesenchymal hybrid intestines developed as grafts (into the coelomic cavity of chick embryos or under the kidney capsule of adult mice) led to the conclusion that HSPG molecules located in the basement membrane of the developing intestine were produced exclusively by the epithelial cells. These data emphasize the notion already gained from previous studies, in which type IV collagen has been shown to be produced by mesenchymal cells (Simon-Assmann, P., F. Bouziges, C. Arnold, K. Haffen, and M. Kedinger. 1988. Development (Camb.). 102:339-347), that epithelial-mesenchymal interactions play an important role in the formation of a complete basement membrane.

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