Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simple three-enzyme treatment of collagenase, dispase and hyaluronidase on finely minced chick oviduct yields clumps of 50-150 cells. These cells attach to collagen-treated dishes and survive in culture for at least 2 weeks without subculturing. Oviduct cell cultures can also be induced to grow. Estradiol or epidermal growth factor (EGF) induce a 40% increase in cells in 4 days when cultures are grown in serum levels that do not support growth. Serum from estrogen-stimulated chicks promotes rapid cellular proliferation (doubling times of 1-2 days). Sera from estrogen withdrawn chicks, laying hen or horse do not support as rapid proliferation. The oviduct growth-promoting factors in serum from estrogen-stimulated chicks are not steroids or fibroblast growth factors (FGF). Removal of steroids from these sera by charcoal treatment or delipidization does not decrease the rate of growth. The addition of 1-100 nM estradiol does not increase a serum's ability to promote growth. Purified FGF or platelet-derived growth factor (PDGF) do not induce oviduct proliferation. These results were reproduced in oviduct cell cultures started from estrogen-stimulated and withdrawn chicks as well as laying hens. Thus the factors in serum from estrogen-stimulated chicks that promote rapid oviduct growth are induced by estrogen treatments in vivo, but do not seem to be only steroids.
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PMID:The chick oviduct in tissue culture. I. Initial characterization of growing primary oviduct tissue cultures. 633 49

The surface of rat arterial smooth muscle cells was characterized with respect to some of its chemical and functional properties. The effects of selective enzymic degradations (hyaluronidase, chondroitinases, heparitinase or neuraminidase) on [35S]sulphate-prelabelled cells and on binding sites for cationized ferritin (CF) were examined to assess the presence and relative importance of individual species of macromolecules on the cell surface. The results indicate that about half of the strongly anionic sites on the cell surface (binding CF at pH 2.0) could be ascribed to sulphate groups of glycosaminoglycans and about half to carboxyl groups of sialic acid residues in glycoproteins and/or glycolipids. Weaker anionic sites (binding CF at pH 7.0) largely originated from carboxyl groups of glycosaminoglycans. Chondroitin sulphate and heparan sulphate were the main glycosaminoglycans. The surface of cells from young animals showed a higher glycosaminoglycan and a lower sialic acid content than that of cells from adult animals. Continuous treatment of the cultures with neuraminidase stimulated serum-induced initiation of DNA synthesis, while treatment with hyaluronidase or heparitinase inhibited it. Addition of hyaluronic acid, heparin or heparan sulphate to the culture medium inhibited initiation of DNA synthesis as well as cell proliferation. The effect was more marked in cultures of cells from young animals than from adults, although the latter cells were found to grow at a higher rate and to higher densities. These results suggest a role for cell-surface and pericellular glycoconjugates in growth regulation. A possible mechanism of action is that these molecules, due to their anionic charge or by steric exclusion, interfere with the binding of platelet-derived growth factor, a highly cationic polypeptide, to its cell-surface receptor.
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PMID:Cell surface components and growth regulation in cultivated arterial smooth muscle cells. 642 Apr 21

Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that soluble effectors produced by bone marrow-derived cells may modulate the function of the decidual cells. To investigate this, a cell purification protocol was devised that involved digestion of first-trimester decidua with collagenase and hyaluronidase to produce a mixed stromal cell suspension from which the bone marrow-derived cells were removed using immunomagnetic beads coated with anti-CD45. The resulting stromal cells were maintained in culture in the presence of progesterone and were found to produce PRL. The effect of a panel of cytokines on PRL production was examined. Tumor necrosis factors-alpha and -beta had a dose-dependent inhibitory effect, and tumor necrosis factor receptors were identified on the cells. Interleukin 1 alpha and 1 beta, platelet-derived growth factor, and transforming growth factor-beta 1 were also found to inhibit PRL production, and platelet-derived growth factor and transforming growth factor-beta 1 stimulated cell proliferation. These findings suggest an interaction between the immune and endocrine systems in regulating the maternal environment of early pregnancy.
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PMID:Comment: effect of cytokines on prolactin production by human decidual stromal cells in culture: studies using cells freed of bone marrow-derived contaminants. 798 96

In this study we examined the capacity of normal human mesothelial (NHM) cells and human malignant mesothelioma cells to form hyaluronan-containing pericellular matrices or "coats." The assembly of the pericellular coats was visualized by a particle exclusion assay. We found that large hyaluronan-containing coats were formed around NHM cells whereas their transformed counterparts had no or very limited coats. The coats were removed by treatment with Streptomyces hyaluronidase, which specifically degrades hyaluronan. NHM cells exhibited hyaluronan-containing pericellular matrix within 5 h after seeding. The formation of the coats was stimulated by platelet-derived growth factor and epidermal growth factor. Interestingly, the assembly of the hyaluronan-dependent pericellular matrices was inhibited by the addition of hyaluronan dodecasaccharides. The inhibitory effect on the formation of the coats was due to a destabilization of pericellular matrix and not due to an inhibitory effect of hyaluronan dodecasaccharides on hyaluronan synthesis. In contrast, hyaluronan hexasaccharides, an inhibitor of the interaction between polymeric hyaluronan and its cell surface receptors, had no effect on the size of the coat. Thus, our results are compatible with the possibility that the pericellular matrix surrounding NHM cells consists of newly synthesized hyaluronan which is extruded from the cell and independent of hyaluronan receptors on the cell surface. The coat seems to be stabilized by interactions (hyaluronan-hyaluronan or hyaluronan-protein bridges) which can be prevented by hyaluronan dodecasaccharides.
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PMID:Synthesis and assembly of the hyaluronan-containing coats around normal human mesothelial cells. 837 71

Previous studies have indicated that fetal skin fibroblasts display an elevated level of migratory activity compared to adult cells and that this may result from inherent differences in the production of hyaluronan (HA) by these cells. Data presented in this communication indicate that the elevated level of fetal fibroblast migration into 3D-collagen gels and HA synthesis by these cells were not affected by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF). In contrast, both cell migration and HA synthesis by fetal fibroblasts were inhibited by transforming growth factor-betal (TGF-beta1). Adult fibroblasts responded to these cytokines in a distinct fashion: i.e. cell migration and HA synthesis were stimulated by EGF, PDGF, aFGF and bFGF, but remained unaffected by TGF-beta1. Gel-filtration chromatography revealed that these effects of cytokines on HA synthesis were predominantly confined to the production of high molecular mass (>106 kDa) species. Co-exposure of cells to both cytokines and Streptomyces hyaluronidase revealed that (1) the elevated migration of control fetal fibroblasts was inhibited by hyaluronidase, (2) this inhibition was partially restored by co-exposure to EGF, PDGF, aFGF and bFGF, but remained unaffected by TGF-beta1, (3) the migration of control adult fibroblasts was unaffected by hyaluronidase and partially stimulated by EGF, aFGF and bFGF (when compared to the effects of these cytokines on cells cultured in the absence of hyaluronidase) and (4) neither PDGF nor TGF-beta1 affected the migration of hyaluronidase-treated adult cells. Linear regression analysis revealed a significant correlation between cell migration and HA synthesis by both fetal and adult fibroblasts in the presence and absence of cytokines (r2=0.9277, P<0.0001), with the exception of adult fibroblasts exposed to PDGF. Taken together, these findings suggest that (1) the migration of fetal and adult fibroblasts is differentially modulated by exogenous cytokines and (2) with the possible exception of the effects of PDGF on adult fibroblasts, cytokine-induced modulation of cell migration appears to utilise both HA-dependent and HA-independent pathways.
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PMID:Differential response of fetal and adult fibroblasts to cytokines: cell migration and hyaluronan synthesis. 910 75

The roles of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in vein disease and aging were investigated. Smooth muscle cells from human saphenous veins were cultured. The age dependence of bFGF and PDGF activation of the smooth muscle cell proliferation was determined, and the bFGF and PDGF contents in vein wall homogenates were measured by an enzyme-linked sorbent assay. There were morphological alterations in the cells with more polygonal and polynucleated cells in cultures from aged donors, similar to those observed in vitro in aged cell cultures. Some cultures did not reach confluency after the tenth passage, suggesting early decay of the cultures from diseased veins. bFGF and PDGF stimulated the proliferation of the vein smooth muscle cells, but only in cultures treated with hyaluronidase. This stimulation decreased with the age of the donor. The amount of the two growth factors in human vein walls decreased with donor age. The amount of bFGF decreased faster (slope: 3.3138 ng/mg DNA/year) than that of PDGF (slope: 1.021 ng/mg DNA/year). This results in an age-dependent change in the bFGF/PDGF ratio from 4 mol/mol at the age of 20 years to 1 mol/mol at the age of 80. These growth factors also modulate the synthesis of extracellular matrix components. The continuous change in the bFGF/PDGF ratio may alter the composition of the extracellular matrix of the vein wall during aging and thus its susceptibility to varicose disease.
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PMID:Preliminary data on the age-dependent decrease in basic fibroblast growth factor and platelet-derived growth factor in the human vein wall and in their influence on cell proliferation. 943 9

The formation of atherosclerotic lesions is characterized by invasion of vascular smooth muscle cells (VSMC) into the tunica intima of the arterial wall and subsequently by increased proliferation of VSMC, a process apparently restricted to the intimal layer of blood vessels. Both events are preceded by the pathological overexpression of several growth factors, such as platelet-derived growth factor (PDGF) which is a potent mitogen for VSMC and can induce their chemotaxis. PDGF is generally not expressed in the normal artery but it is upregulated in atherosclerotic lesions. We have previously shown that PDGF-BB specifically stimulates proliferating VSMC to secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence regarding the biological functions of this glycan. We observed that HA-340 inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent manner and enhanced the PDGF-dependent invasion of VSMC through a basement membrane barrier. These effects were abolished following treatment of HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent invasion of VSMC coincided with increased secretion of the 72-kDa type IV collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. HA-340 did not exert any chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF gradient. In human atheromatic aortas, we found that HA-340 is expressed with a negative concentration gradient from the tunica media to the tunica intima and the atheromatic plaque. Our findings suggest that HA-340 may be linked to the pathogenesis of atherosclerosis, by modulating VSMC proliferation and invasion.
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PMID:A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration. 963 43

The accumulation of hyaluronan (HA) and the HA-binding proteoglycan versican around smooth muscle cells in lesions of atherosclerosis suggests that together these molecules play an important role in the events of atherogenesis. In this study we have examined the formation of HA- and versican-rich pericellular matrices by human aortic smooth muscle cells in vitro, using a particle-exclusion assay, and the role of the pericellular matrix in cell proliferation and migration. The structural dependence of the pericellular matrix on HA can be demonstrated by the complete removal of the matrix with Streptomyces hyaluronidase. The presence of versican in the pericellular matrix was confirmed immunocytochemically. By electron microscopy, the cell coat was seen as a tangled network of hyaluronidase-sensitive filaments decorated with ruthenium red-positive proteoglycan granules. Ninety percent of migrating cells in wounded cultures, and virtually all mitotic cells, displayed abundant HA- and versican-rich coats. Time-lapse video imaging revealed that HA- and versican-rich pericellular matrix formation is dynamic and rapid, and coordinated specifically with cell detachment and mitotic cell rounding. HA oligosaccharides, which inhibit the binding of HA to the cell surface and prevent pericellular matrix formation, significantly reduced proliferation and migration in response to platelet-derived growth factor, whereas larger HA fragments and high molecular weight HA had no effect. Treatment with HA oligosaccharides also led to changes in cell shape from a typical fusiform morphology to a more spread and flattened appearance. These data suggest that organization of HA- and versican-rich pericellular matrices may facilitate migration and mitosis by diminishing cell surface adhesivity and affecting cell shape through steric exclusion and the viscous properties of HA proteoglycan gels.
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PMID:Formation of hyaluronan- and versican-rich pericellular matrix is required for proliferation and migration of vascular smooth muscle cells. 1019 29

The glycosaminoglycan hyaluronan is important in many tissuerepair processes. We have investigated the synthesis of hyaluronan in a panel of cell lines of fibroblastic and epithelial origin in response to PDGF (platelet-derived growth factor)-BB and other growth factors. Human dermal fibroblasts exhibited the highest hyaluronan-synthesizing activity in response to PDGF-BB. Analysis of HAS (hyaluronan synthase) and HYAL (hyaluronidase) mRNA expression showed that PDGF-BB treatment induced a 3-fold increase in the already high level of HAS2 mRNA, and increases in HAS1 and HYAL1 mRNA, whereas the levels of HAS3 and HYAL2 mRNA were not affected. Furthermore, PDGF-BB also increased the amount and activity of HAS2 protein, but not of HYAL1 and HYAL2 proteins. Using inhibitors for MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 1/2] (U0126) and for PI3K (phosphoinositide 3-kinase) (LY294002), as well as the SN50 inhibitor, which prevents translocation of the active NF-kappaB (nuclear factor kappaB) to the nucleus, we observed a complete inhibition of both HAS2 transcriptional activity and hyaluronan synthesis, whereas inhibitors of other signalling pathways were without any significant effect. TGF-beta1 (transforming growth factor-beta1) did not increase the activity of hyaluronan synthesis in dermal fibroblasts, but increased the activity of HYALs. Importantly, inhibition of hyaluronan binding to its receptor CD44 by the monoclonal antibody Hermes-1, inhibited PDGF-BB-stimulated [3H]thymidine incorporation of dermal fibroblasts. We conclude that the ERK MAPK and PI3K signalling pathways are necessary for the regulation of hyaluronan synthesis by PDGF-BB, and that prevention of its binding to CD44 inhibits PDGF-BB-induced cell growth.
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PMID:Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB. 1732 21

Natural carbohydrate is a class of underexplored polymers for gene delivery. The noninflammatory and nonimmunogenic properties of hyaluronan (hyaluronic acid, HA) are important in clinical situations. It has a role in wound repair and has great lubricating ability. Moreover, the presence of hyaluronidase in vivo enables any vehicle fabricated from HA to be degraded by enzyme-mediated erosion. When DNA is entrapped in a cross-linked HA vehicle, HA-DNA fragments are released on digestion by hyaluronidase. These fragments could serve both as microcarriers of DNA and its protective mechanism. This protocol describes preparation of water-insoluble HA-DNA matrices and films designed for clinical applications, and assays for verification of their bioactivities. Plasmid DNA (pDNA) encoding platelet-derived growth factor (PDGF) is coupled to the matrices that could be implanted into chronic wounds to accelerate their healing. pDNA encoding hyaluronan synthase 2 (HAS2) is coupled to the film that could initially serve as a physical barrier and subsequently a pDNA reservoir for sustaining HAS2 transfection. This would lead to continual HA production for preventing postsurgical adhesion.
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PMID:Preparation of hyaluronan-DNA matrices and films. 2302 77


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