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Keratan sulfate

About: Keratan sulfate is a(n) research topic. Over the lifetime, 1253 publication(s) have been published within this topic receiving 57984 citation(s). The topic is also known as: keratan sulfate & KS.


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Journal ArticleDOI
TL;DR: A crucial role is established for lumican in the regulation of collagen assembly into fibrils in various connective tissues and the development of a highly organized collagenous matrix and corneal transparency.
Abstract: Lumican, a prototypic leucine-rich proteoglycan with keratan sulfate side chains, is a major component of the cornea, dermal, and muscle connective tissues. Mice homozygous for a null mutation in lumican display skin laxity and fragility resembling certain types of Ehlers-Danlos syndrome. In addition, the mutant mice develop bilateral corneal opacification. The underlying connective tissue defect in the homozygous mutants is deregulated growth of collagen fibrils with a significant proportion of abnormally thick collagen fibrils in the skin and cornea as indicated by transmission electron microscopy. A highly organized and regularly spaced collagen fibril matrix typical of the normal cornea is also missing in these mutant mice. This study establishes a crucial role for lumican in the regulation of collagen assembly into fibrils in various connective tissues. Most importantly, these results provide a definitive link between a necessity for lumican in the development of a highly organized collagenous matrix and corneal transparency.

662 citations

Journal ArticleDOI
TL;DR: It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth and its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response.
Abstract: Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of 125I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 X 10(12) binding sites/mm2 ECM with an apparent kD of 610nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 micrograms/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 micrograms/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there was little or no release of FGF by modified nonanticoagulant heparins such as totally desulfated heparin, N-desulfated heparin, and N-acetylated heparin. FGF released from ECM was biologically active, as indicated by its stimulation of cell proliferation and DNA synthesis in vascular endothelial cells and 3T3 fibroblasts. Similar results were obtained in studies on release of endogenous FGF-like mitogenic activity from Descemet's membranes of bovine corneas. It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth. Whereas ECM-bound FGF may be prevented from acting on endothelial cells, its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response.

586 citations

Journal ArticleDOI
TL;DR: Proteoglycan monomer (D1) and aggregate (A1) preparations were isolated from 4 M guanidinium chloride extracts of the Swarm rat chondrosarcoma and contained only small proteoglycan fragments, indicating that extensive enzymatic degradation had occurred.
Abstract: Proteoglycan monomer (D1) and aggregate (A1) preparations were isolated from 4 M guanidinium chloride extracts of the Swarm rat chondrosarcoma. When EDTA, 6-aminohexanoic acid, and benzamidine were present in the solutions, the D1 preparation contained a single component (SO = 23 S), and the A1 preparation contained 30% monomer (SO = 23 S) and 70 percent aggregate (SO = 111 S). In the absence of EDTA, 6-aminohexanoic acid, and benzamidine, the A1 preparations contained only small proteoglycan fragments, indicating that extensive enzymatic degradation had occurred. The composition of the proteoglycan monomer was different from that of proteoglycan monomer preparations from normal hyaline cartilages in that it did not contain keratan sulfate and chondroitin 6-sulfate; only chondroitin 4-sulfate was found. The A1 preparation from the chondrosarcoma contained only one link protein, which was like the smaller (molecular weight of 40,000) of the two link proteins present in A1 preparations from bovine nasal cartilage. When the A1 preparation from the chondrosarcoma was treated with chondroitinase ABC and trypsin and the digest was chromatographed on Sepharose 2B, a complex was isolated which contained the link protein and the segments of the protein core from the hyaluronic acid-binding region of the proteoglycan molecules.

542 citations

Journal ArticleDOI
TL;DR: Evidence is presented which suggests that the hyaluronic acid-proteoglycan interactions described by Hardingham and Muir ((1972) Biochim.
Abstract: Viscosimetric and centrifugal analyses of nasal and tracheal proteoglycan preparations indicate that: a, the proteoglycan molecules from both cartilages have very similar physical properties (limiting viscosity numbers of 140 and 145 ml per g and s0 values of 25 and 20 S, respectively); b, about 80% of the proteoglycan molecules in each preparation can form aggregates; and c, the aggregates are much larger in nasal than in tracheal preparations (s0 values of 93 and 43 S, respectively). Hyaluronic acid is present at a concentration of 0.4 to 0.8% (w/w) in nasal proteoglycan aggregate preparations. Evidence is presented which suggests that the hyaluronic acid-proteoglycan interactions described by Hardingham and Muir ((1972) Biochim. Biophys. Acta 279, 401) are involved in aggregate formation and that the relative sizes of the aggregates are probably determined by the relative sizes of the hyaluronic acid molecules. Mild proteolysis of proteoglycan aggregates with papain removes the chondroitin sulfate and keratan sulfate from the aggregates while leaving about 25% of the total protein still bound to hyaluronic acid. This bound protein fraction was separated from the hyaluronic acid by chromatography on Sephadex G-200 with 4 m guanidine hydrochloride as the solvent. Polyacrylamide gel electrophoresis indicated that this fraction contains two proteins (molecular weights approximately 40,000 and 65,000) both of which are reduced to smaller peptide fragments when treated with β-mercaptoethanol. The two proteins retain their ability to bind to hyaluronic acid. The interactions between the proteins and the hyaluronic acid in the intact aggregates partially protect the hyaluronic acid from digestion with bacterial chondroitinase.

534 citations

Journal ArticleDOI
TL;DR: It is suggested that HCII is the only thrombin inhibitor in human plasma that can be activated by dermatan sulfate.
Abstract: We have tested the ability of various glycosaminoglycans to increase the rate of inhibition of thrombin by heparin cofactor II (HCII) and by antithrombin III (ATIII) isolated from human plasma. Heparin, dermatan sulfate, and heparan sulfate from bovine liver (in order of decreasing activity) activated HCII. In contrast, only heparin and bovine liver heparan sulfate activated ATIII, whereas dermatan sulfate was inactive at concentrations less than or equal to 1 mg/ml. Heparan sulfate from human aorta, chondroitin 4-sulfate, chondroitin 6-sulfate, keratan sulfate, and hyaluronic acid had little or no activity with either HCII or ATIII. The second order rate constant for the thrombin-HCII reaction reached a maximum value of 6.4 X 10(8) M-1 min-1 in the presence of 250-500 micrograms/ml of dermatan sulfate compared to 3.8 X 10(8) M-1 min-1 in the presence of 40-80 micrograms/ml of heparin. When 125I-thrombin was incubated with plasma in the presence of greater than or equal to 100 micrograms/ml of dermatan sulfate, the protease became complexed exclusively with HCII, suggesting that HCII is the only thrombin inhibitor in human plasma that can be activated by dermatan sulfate.

425 citations

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20217
20209
201912
201812
201715
201613