Syndecan 3

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David J. Carey - One of the best experts on this subject based on the ideXlab platform.

  • Differential expression of proteoglycans at central and peripheral nodes of Ranvier.
    Glia, 2005
    Co-Authors: Carmen V. Melendez-vasquez, Ofer Reizes, David J. Carey, George Zanazzi, Patrice Maurel, James L. Salzer
    Abstract:

    The nodes of Ranvier are regularly spaced gaps between myelin sheaths that are markedly enriched in voltage-gated sodium channels and associated proteins. Myelinating glia play a key role in promoting node formation, although the requisite glial signals remain poorly understood. In this study, we have examined the expression of glial proteoglycans in the peripheral and central nodes. We report that the heparan sulfate proteoglycan, Syndecan-3, becomes highly enriched with PNS node formation; its ligand, collagen V, is also concentrated at the PNS nodes and at lower levels along the abaxonal membrane. The V1 isoform of versican, a chondroitin sulfate proteoglycan, is also present in the nodal gap. By contrast, CNS nodes are enriched in versican isoform V2, but not Syndecan-3. We have examined the molecular composition of the PNS nodes in Syndecan-3 knockout mice. Nodal components are normally expressed in mice deficient in Syndecan-3, suggesting that it has a nonessential role in the organization of nodes in the adult. These results indicate that the molecular composition and extracellular environment of the PNS and CNS nodes of Ranvier are significantly distinct.

  • Matrix metalloproteinase-dependent shedding of Syndecan-3, a transmembrane heparan sulfate proteoglycan, in Schwann cells.
    Journal of Neuroscience Research, 2003
    Co-Authors: Vinod K Asundi, Robert Erdman, Richard C. Stahl, David J. Carey
    Abstract:

    Schwann cells transiently express the transmembrane heparan sulfate proteoglycan Syndecan-3 during the late embryonic and early postnatal periods of peripheral nerve development. Neonatal rat Schwann cells released soluble Syndecan-3 into the culture medium by a process that was blocked by inhibition of endogenous matrix metalloproteinase activity. When Schwann cells were plated on a substratum that binds Syndecan-3, the released proteoglycan bound to the substratum adjacent to the cell border. Membrane-anchored Syndecan-3 was concentrated in actin-containing filopodia that projected from the lateral edges of the Schwann cell membrane. Membrane shedding was specific for Syndecan-3 and was not observed for the related proteoglycan Syndecan-1. Analysis of Schwann cells transfected with wild-type and chimeric Syndecan-1 and Syndecan-3 cDNAs revealed that membrane shedding was a property of the Syndecan-3 ectodomain. Inhibition of Syndecan-3 release significantly enhanced Schwann cell adhesion and process extension on dishes coated with the non-collagenous N-terminal domain of α4(V) collagen, which binds Syndecan-3 and mediates heparan sulfate-dependent Schwann cell adhesion. Matrix metalloproteinase-dependent Syndecan-3 shedding was also observed in newborn rat peripheral nerve tissue. Syndecan-3 shedding in peripheral nerve tissue was age specific, and was not observed during later stages of postnatal nerve development. These results demonstrate that Schwann cell Syndecan-3 is subject to matrix metalloproteinase-dependent membrane processing, which modulates the biological function of this proteoglycan. © 2003 Wiley-Liss, Inc.

  • Syndecan-3 and perlecan are differentially expressed by progenitors and mature oligodendrocytes and accumulate in the extracellular matrix.
    Journal of Neuroscience Research, 2002
    Co-Authors: Susan Winkler, David J. Carey, Richard C. Stahl, Rashmi Bansal
    Abstract:

    Oligodendrocyte progenitors originate in the subventricular zone, proliferate, migrate to their final destinations, differentiate, and interact with axons to produce multilamellar myelin sheaths. These processes are regulated by a variety of environmental signals, including growth factors, the extracellular matrix, and adhesion molecules. Heparan sulfate proteoglycans are premier candidates as participants in this regulation by virtue of their structural diversity and their capacity to function as coreceptors for both growth factors and extracellular matrix molecules. Consistently with this, we have previously shown that oligodendrocyte progenitors are unable to proliferate in response to fibroblast growth factor-2 (FGF-2) in the absence of sulfated heparan sulfate proteoglycan. Here we show that members of three families of heparan sulfate proteoglycans, Syndecan, perlecan, and glypican, are developmentally and posttranscriptionally regulated during oligodendrocyte-lineage progression: Syndecan-3 is synthesized by oligodendrocyte progenitors (but not terminally differentiated oligodendrocytes) and is up-regulated by FGF-2; perlecan synthesis increases as oligodendrocytes undergo terminal differentiation; glypican-1 is expressed by both progenitors and differentiated oligodendrocytes. Astrocytes express glypican-1 and perlecan but not Syndecan-3. All three of these heparan sulfate proteoglycans are shed from the cell surface and bind to specific substrates. The developmentally regulated expression of these heparan sulfate proteoglycans is indicative of their participation in events involving growth factor receptors and the extracellular matrix that may regulate oligodendrocyte progenitor proliferation, migration, and adhesion phenomena.

  • schwann cell adhesion to a novel heparan sulfate binding site in the n terminal domain of α4 type v collagen is mediated by Syndecan 3
    Journal of Biological Chemistry, 2002
    Co-Authors: Robert Erdman, Richard C. Stahl, Michael A. Chernousov, Katrina Rothblum, David J. Carey
    Abstract:

    Abstract Previously we reported that type V collagen synthesized by Schwann cells inhibits the outgrowth of axons from rat embryo dorsal root ganglion neurons but promotes Schwann cell migration (Chernousov, M. A., Stahl, R. C., and Carey, D. J. (2001) J. Neurosci. 21, 6125–6135). Analysis of Schwann cell adhesion and spreading on dishes coated with various type V collagen domains revealed that Schwann cells adhered effectively only to the non-collagenous N-terminal domain (NTD) of the α4(V) collagen chain. Schwann cell adhesion to α4(V)-NTD induced actin cytoskeleton assembly, tyrosine phosphorylation, and activation of the Erk1/Erk2 protein kinases. Adhesion to α4(V)-NTD is cell type-specific because rat fibroblasts failed to adhere to dishes coated with this polypeptide. Schwann cell adhesion and spreading on α4(V)-NTD was strongly inhibited by soluble heparin (IC50∼30 ng/ml) but not by chondroitin sulfate. Analysis of the heparin binding activities of a series of recombinant α4(V)-NTD fragments and deletion mutants identified a highly basic region (not present in other type V collagen NTD) as the site responsible for high affinity heparin binding. Schwann cells adhered poorly to dishes coated with α4(V)-NTD that lacked the heparin binding site and failed to spread or assemble organized actin-cytoskeletal structures. Soluble α4(V)-NTD polypeptide that contained the heparin binding site inhibited spreading of Schwann cells on dishes coated with α4(V)-NTD. Affinity chromatography of Schwann cell detergent extracts on a column of immobilized α4(V)-NTD resulted in the isolation of Syndecan-3, a transmembrane heparan sulfate proteoglycan. Together, these results suggest that Schwann cells bind to collagen type V via Syndecan-3-dependent binding to a novel high affinity heparin binding site in the α4(V)-NTD.

  • In Vivo Regulation of Syndecan-3 Expression in the Rat Uterus by 17β-Estradiol
    The Journal of biological chemistry, 2001
    Co-Authors: Louise A. Russo, David J. Carey, Stephen P. Calabro, Tracy A. Filler, Russell M. Gardner
    Abstract:

    Abstract The immature rat uterus has been extensively used as an in vivo model system to study the molecular mechanisms of steroid hormone actions. In this study, we demonstrated the regulated expression of Syndecan-3 in the rat uterus by the steroid hormone 17β-estradiol. Administration of a single physiological dose of 17β-estradiol (40 μg/kg) to ovariectomized immature animals induced a rapid and transient increase in uterine Syndecan-3 mRNA. Transcript levels reached a peak elevation of 3-fold above saline control tissues 4 h after hormone administration. Inhibition of message up-regulation by actinomycin D but not cycloheximide indicated a hormone response dependent on RNA transcription but not new protein synthesis. The estrogenic ligands estriol and tamoxifen were also effective at raising Syndecan-3 mRNA levels; however, nonestrogenic ligands, including progesterone, 5α-dihydrotestosterone, and dexamethasone, failed to stimulate a change in mRNA levels. Hormone-induced changes in mRNA led to transient changes in Syndecan-3 protein content and significant alteration in the temporal and spatial expression in endometrial epithelial cells. Collectively, these data show that the steroid hormone 17β-estradiol, regulates transcription of the Syndecan-3 gene in the uterus via an estrogen receptor-dependent mechanism. This estrogen-regulated expression of Syndecan-3 may play an important role in changes in tissue ultrastructure crucial for proper uterine growth.

Robert A. Kosher - One of the best experts on this subject based on the ideXlab platform.

  • heparan sulfate proteoglycans including Syndecan 3 modulate bmp activity during limb cartilage differentiation
    Matrix Biology, 2006
    Co-Authors: Melanie C Fisher, Yingcui Li, Reza M Seghatoleslami, Caroline N Dealy, Robert A. Kosher
    Abstract:

    Bone morphogenetic proteins (BMPs) are involved in multiple aspects of limb development including regulation of cartilage differentiation. Several BMPs bind strongly to heparin, and heparan sulfate proteoglycans (HSPGs) at the cell surface or in the extracellular matrix have recently been implicated as modulators of BMP signaling in some developing systems. Here we have explored the role of HSPGs in regulating BMP activity during limb chondrogenesis by evaluating the effects of exogenous heparan sulfate (HS), heparitinase treatment, and overexpression of the HSPG Syndecan-3 on the ability of BMP2 to modulate the chondrogenic differentiation of limb mesenchymal cells in micromass culture. Exogenous HS dramatically enhances the ability of BMP2 to stimulate chondrogenesis and cartilage specific gene expression, and reduces the concentration of BMP2 needed to stimulate chondrogenesis. Furthermore, HS stimulates BMP2-mediated phosphorylation of Smad1, Smad5, and Smad8, transcriptional mediators of BMP2 signaling, indicating that HS enhances the interaction of BMP2 with its receptors. Pretreatment of micromass cultures with heparitinase to degrade endogenous HSPGs also enhances the chondrogenic activity of BMP2, and reduces the concentration of BMP2 needed to promote chondrogenesis. Taken together these results indicate that exogenous HS or heparitinase enhance the chondrogenic activity of BMP2 by interfering with its interaction with endogenous HSPGs that would normally restrict its interaction with its receptors. Consistent with the possibility that HSPGs are negative modulators of BMP signaling during chondrogenesis, we have found that overexpression of Syndecan-3, which is one of the major HSPGs normally expressed during chondrogenesis, greatly impairs the ability of BMP2 to promote cartilage differentiation. Furthermore, retroviral overexpression of Syndecan-3 inhibits BMP2-mediated Smad phosphorylation in the regions of the cultures in which chondrogenesis is inhibited and in which ectopic Syndecan-3 protein is highly expressed. These results indicate that Syndecan-3 interferes with the interaction of BMP2 with its receptors, and that this interference results in an inhibition of chondrogenesis. Taken together these results indicate that HSPGs including Syndecan-3 normally modulate the strength of BMP signaling during limb cartilage differentiation by limiting the effective concentration of BMP available for signaling.

  • Syndecan-3 in limb skeletal development.
    Microscopy Research and Technique, 1998
    Co-Authors: Robert A. Kosher
    Abstract:

    Syndecan-3 is a member of a family of heparan sulfate proteoglycans that function as extracellular matrix receptors and as co-receptors for growth factors and signalling molecules. A variety of studies indicate that Syndecan-3 is involved in several aspects of limb morphogenesis and skeletal development. Syndecan-3 participates in limb outgrowth and proliferation in response to the apical ectodermal ridge; mediates cell-matrix and/or cell-cell interactions involved in regulating the onset of chondrogenesis; may be involved in regulating the onset of osteogenesis and joint formation and, plays a role in regulating the proliferation of epiphyseal chondrocytes during endochondral ossification.

  • FGF-stimulated outgrowth and proliferation of limb mesoderm is dependent on Syndecan-3.
    Developmental Biology, 1997
    Co-Authors: Caroline N Dealy, M. Reza Seghatoleslami, Deborah Ferrari, Robert A. Kosher
    Abstract:

    The outgrowth of the mesoderm of the developing limb bud in response to the apical ectodermal ridge (AER) is mediated at least in part by members of the FGF family. Recent studies have indicated that FGFs need to interact with heparan sulfate proteoglycans in order to bind to and activate their specific cell surface receptors. Syndecan-3 is an integral membrane heparan sulfate proteoglycan that is highly expressed by the distal mesodermal cells of the chick limb bud that are undergoing proliferation and outgrowth in response to the AER. Here we report that maintenance of high-level Syndecan-3 expression by the subridge mesoderm of the chick limb bud is directly or indirectly dependent on the AER, since its expression is severely impaired in the distal mesoderm of the limb buds of limbless and wingless mutant embryos which lack functional AERs capable of directing the outgrowth of limb mesoderm. We have also found that exogenous FGF-2 maintains a domain of high-level Syndecan-3 expression in the outgrowing mesodermal cells of explants of the posterior mesoderm of normal limb buds cultured in the absence of the AER and in the outgrowing subapical mesoderm of explants of limbless mutant limb buds which lack a functional AER. These results suggest that the domain of high-level Syndecan-3 expression in the subridge mesoderm of normal limb buds is maintained by FGFs produced by the AER. Finally, we report that polyclonal antibodies against a Syndecan-3 fusion protein inhibit the ability of FGF-2 to promote the proliferation and outgrowth of the posterior subridge mesoderm of limb buds cultured in the absence of the AER. These results suggest that Syndecan-3 plays an essential role in limb outgrowth by mediating the interaction of FGFs produced by the AER with the underlying mesoderm of the limb bud.

  • Inhibition of in vitro limb cartilage differentiation by Syndecan‐3 antibodies
    Developmental Dynamics, 1996
    Co-Authors: M. Reza Seghatoleslami, Robert A. Kosher
    Abstract:

    : The transmembrane heparan sulfate proteoglycan Syndecan-3 is transiently expressed in high amounts during the cellular condensation process that characterizes the onset of limb cartilage differentiation. During condensation, limb mesenchymal cells become closely juxtaposed and undergo cell-cell and cell-matrix interactions that are necessary to trigger cartilage differentiation and cartilage-specific gene expression. To test directly the possible involvement of Syndecan-3 in regulating the onset of limb chondrogenesis, we examined the effect of polyclonal antibodies against a Syndecan-3 fusion protein on the chondrogenic differentiation of chick limb mesenchymal cells in micromass culture. Syndecan-3 antiserum elicits a dose-dependent inhibition of the accumulation of Alcian blue-stainable cartilage matrix by high density limb mesenchymal cell micromass cultures (2 x 10(5) cells/10 microliters) and a corresponding reduction in steady-state levels of mRNAs for cartilage-characteristic type II collagen and the core protein of the cartilage proteoglycan aggrecan. In preimmune serum-treated control cultures proliferating cells are limited to the periphery of areas of cartilage matrix deposition, whereas large numbers of proliferating cells are uniformly distributed throughout the undifferentiated cultures supplemented with Syndecan-3 antiserum. Limb mesenchymal cells cultured at lower densities (1 x 10(5) cells/10 microliters) in the presence of preimmune serum form extensive precartilage condensations characterized by the close juxtaposition of rounded cells by day 2 of culture. In contrast, in the presence of Syndecan-3 antiserum, the cells fail to aggregate but rather remain flattened and spatially separated from one another, suggeting that Syndecan-3 antibodies impair the formation of precartilage condensations. These results indicate that Syndecan-3 plays an important role in regulating the onset of limb chondrogenesis, perhaps by mediating the cell-cell and cell-matrix interactions required for condensation and subsequent cartilage differentiation.

  • inhibition of in vitro limb cartilage differentiation by Syndecan 3 antibodies
    Developmental Dynamics, 1996
    Co-Authors: Reza M Seghatoleslami, Robert A. Kosher
    Abstract:

    The transmembrane heparan sulfate proteoglycan Syndecan-3 is transiently expressed in high amounts during the cellular condensation process that characterizes the onset of limb cartilage differentiation. During condensation, limb mesenchymal cells become closely juxtaposed and undergo cell-cell and cell-matrix interactions that are necessary to trigger cartilage differentiation and cartilage-specific gene expression. To test directly the possible involvement of Syndecan-3 in regulating the onset of limb chondrogenesis, we examined the effect of polyclonal antibodies against a Syndecan-3 fusion protein on the chondrogenic differentiation of chick limb mesenchymal cells in micromass culture. Syndecan-3 antiserum elicits a dose-dependent inhibition of the accumulation of Alcian blue-stainable cartilage matrix by high density limb mesenchymal cell micromass cultures (2 x 10(5) cells/10 microliters) and a corresponding reduction in steady-state levels of mRNAs for cartilage-characteristic type II collagen and the core protein of the cartilage proteoglycan aggrecan. In preimmune serum-treated control cultures proliferating cells are limited to the periphery of areas of cartilage matrix deposition, whereas large numbers of proliferating cells are uniformly distributed throughout the undifferentiated cultures supplemented with Syndecan-3 antiserum. Limb mesenchymal cells cultured at lower densities (1 x 10(5) cells/10 microliters) in the presence of preimmune serum form extensive precartilage condensations characterized by the close juxtaposition of rounded cells by day 2 of culture. In contrast, in the presence of Syndecan-3 antiserum, the cells fail to aggregate but rather remain flattened and spatially separated from one another, suggeting that Syndecan-3 antibodies impair the formation of precartilage condensations. These results indicate that Syndecan-3 plays an important role in regulating the onset of limb chondrogenesis, perhaps by mediating the cell-cell and cell-matrix interactions required for condensation and subsequent cartilage differentiation.

Ofer Reizes - One of the best experts on this subject based on the ideXlab platform.

  • Syndecan-3 is selectively pro-inflammatory in the joint and contributes to antigen-induced arthritis in mice
    Arthritis Research & Therapy, 2014
    Co-Authors: Oksana Kehoe, Ofer Reizes, Andrew D. Eustace, Sophie King, Neena Kalia, Charlotte Boyes, Anwen Sian Williams, Angela Margaret Patterson, Jim Middleton
    Abstract:

    Introduction Syndecans are heparan sulphate proteoglycans expressed by endothelial cells. Syndecan-3 is expressed by synovial endothelial cells of rheumatoid arthritis (RA) patients where it binds chemokines, suggesting a role in leukocyte trafficking. The objective of the current study was to examine the function of Syndecan-3 in joint inflammation by genetic deletion in mice and compare with other tissues.

  • Enhanced anorexigenic signaling in lean obesity resistant Syndecan-3 null mice.
    Neuroscience, 2010
    Co-Authors: Qiao Zheng, Stephen C. Benoit, Erzsebet Borok, Marya Shanabrough, Tamas L. Horvath, Deborah J Clegg, Ofer Reizes
    Abstract:

    Abstract Obesity is associated with increased risk of diabetes, cardiovascular disease and several types of cancers. The hypothalamus is a region of the brain critical in the regulation of body weight. One of the critical and best studied hypothalamic circuits is comprised of the melanocortinergic orexigenic agouti-related protein (AgRP) and anorexigenic α-melanocyte stimulating hormone (α-MSH) neurons. These neurons project axons to the same hypothalamic target neurons and balance each other's activity leading to body weight regulation. We previously showed that the brain proteoglycan Syndecan-3 regulates feeding behavior and body weight, and Syndecan-3 null (SDC-3 −/− ) mice are lean and obesity resistant. Here we show that the melanocortin agonist Melanotan II (MTII) potently suppresses food intake and activates the hypothalamic paraventricular nuclei (PVN) in SDC-3 −/− mice based on c-fos immunoreactivity. Interestingly, we determined that the AgRP neuropeptide is reduced in the PVN of SDC-3 −/− mice compared to wild type mice. In contrast, neuropeptide Y, coexpressed in the AgRP neuron, is not differentially expressed nor is the counteracting neuropeptide α-MSH. These findings are unprecedented and indicate that AgRP protein localization can be selectively regulated within the hypothalamus resulting in altered neuropeptide response and tone.

  • The role of Syndecans in the regulation of body weight and synaptic plasticity.
    The International Journal of Biochemistry & Cell Biology, 2008
    Co-Authors: Ofer Reizes, Stephen C. Benoit, Deborah J Clegg
    Abstract:

    Body weight is tightly regulated by a feedback mechanism involving peripheral adiposity signals and multiple central nervous system neurotransmitter pathways. Despite the tight regulation of body weight there is an increase in the prevalence of obesity and overweight in Western society. Obesity and overweight are conditions of excess body weight stored as fat. Syndecan-3, a member of the Syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel a regulator of feeding behavior and body weight. Syndecans are extracellular matrix molecules (ECMs) that modulate cell adhesion, cell-cell interactions and ligand-receptor interactions. The finding that Syndecan-3 can regulate body weight is novel and provides a unique link between the extracellular matrix and body weight regulatory mechanisms. Uniquely, hormones such as leptin previously thought only to regulate body weight by modulating neuropeptide levels, have now been demonstrated to regulate neuronal plasticity in the hypothalamus. ECMs and Syndecans have long been recognized as regulators of plasticity. Therefore, this review will focus on highlighting the role of Syndecans and in particular Syndecan-3 in neuronal development and synaptic organization and how these processes may integrate body weight regulation. As part of this review, we will highlight how Syndecan-3 can mediate the activity of adiposity signals, such as leptin, and facilitate changes in neuronal plasticity.

  • A role for Syndecan-3 in the melanocortin regulation of energy balance.
    Peptides, 2006
    Co-Authors: Ofer Reizes, Deborah J Clegg, April D. Strader, Stephen C. Benoit
    Abstract:

    Since the discovery that central melanocortin peptides play an important role in the control of body weight, an impressive amount of research has focused on understanding this complex neuroendocrine system. However, this research has also uncovered new complexities. One of these complexities is the recently discovered putative melanocortin "co-receptor," Syndecan-3. In this review, we present an overview of the biology and potential functions of Syndecan-3 and describe a novel hypothesis for its regulation of energy balance.

  • Differential expression of proteoglycans at central and peripheral nodes of Ranvier.
    Glia, 2005
    Co-Authors: Carmen V. Melendez-vasquez, Ofer Reizes, David J. Carey, George Zanazzi, Patrice Maurel, James L. Salzer
    Abstract:

    The nodes of Ranvier are regularly spaced gaps between myelin sheaths that are markedly enriched in voltage-gated sodium channels and associated proteins. Myelinating glia play a key role in promoting node formation, although the requisite glial signals remain poorly understood. In this study, we have examined the expression of glial proteoglycans in the peripheral and central nodes. We report that the heparan sulfate proteoglycan, Syndecan-3, becomes highly enriched with PNS node formation; its ligand, collagen V, is also concentrated at the PNS nodes and at lower levels along the abaxonal membrane. The V1 isoform of versican, a chondroitin sulfate proteoglycan, is also present in the nodal gap. By contrast, CNS nodes are enriched in versican isoform V2, but not Syndecan-3. We have examined the molecular composition of the PNS nodes in Syndecan-3 knockout mice. Nodal components are normally expressed in mice deficient in Syndecan-3, suggesting that it has a nonessential role in the organization of nodes in the adult. These results indicate that the molecular composition and extracellular environment of the PNS and CNS nodes of Ranvier are significantly distinct.

Enrique Brandan - One of the best experts on this subject based on the ideXlab platform.

  • Heparan sulfate proteoglycans are increased during skeletal muscle regeneration: requirement of Syndecan-3 for successful fiber formation
    Journal of Cell Science, 2004
    Co-Authors: Juan Carlos Casar, Hugo C. Olguín, Claudio Cabello-verrugio, Rebeca Aldunate, Nibaldo C. Inestrosa, Enrique Brandan
    Abstract:

    Skeletal muscle regeneration is a highly complex and regulated process that involves muscle precursor proliferation and differentiation and probably requires the participation of heparin binding growth factors such as FGFs, HGF and TGFβ. Heparan sulfate proteoglycans, key components of cell-surfaces and ECM, modulate growth factor activities and influence cell growth and differentiation. Their expression in forming muscle masses during development and in cell culture, suggest their participation in the regulation of myogenesis. In the present study, heparan sulfate proteoglycan expression in skeletal muscle regeneration induced by barium chloride injection was evaluated. Expression of muscle differentiation markers and neuromuscular junction (NMJ) components was characterized. Immunoblots with anti-Δ-heparan sulfate antibody showed that four major species - perlecan, glypican, Syndecan-3 and Syndecan-4 - were transiently up-regulated. The first three were detected at the surface or basement membranes of newly formed myotubes by specific indirect immunofluorescence. Syndecan-3, a satellite cell marker, showed the earliest and most significant increase. Experiments involving myoblast grafting into regenerating muscle showed that C2C12 cell clones, with inhibited Syndecan-3 expression resulting from antisense transfection, presented a normal proliferation rate but an impaired capacity to fuse and form skeletal muscle fibers. These data constitute the first in vivo evidence suggesting the requirement of a specific heparan sulfate proteoglycan for successful skeletal muscle regeneration.

  • Heparan sulfate proteoglycans are increased during skeletal muscle regeneration: requirement of Syndecan-3 for successful fiber formation.
    Journal of cell science, 2003
    Co-Authors: Juan Carlos Casar, Claudio Cabello-verrugio, Rebeca Aldunate, Nibaldo C. Inestrosa, Hugo Olguin, Enrique Brandan
    Abstract:

    Skeletal muscle regeneration is a highly complex and regulated process that involves muscle precursor proliferation and differentiation and probably requires the participation of heparin binding growth factors such as FGFs, HGF and TGFbeta. Heparan sulfate proteoglycans, key components of cell-surfaces and ECM, modulate growth factor activities and influence cell growth and differentiation. Their expression in forming muscle masses during development and in cell culture, suggest their participation in the regulation of myogenesis. In the present study, heparan sulfate proteoglycan expression in skeletal muscle regeneration induced by barium chloride injection was evaluated. Expression of muscle differentiation markers and neuromuscular junction (NMJ) components was characterized. Immunoblots with anti-Delta-heparan sulfate antibody showed that four major species--perlecan, glypican, Syndecan-3 and Syndecan-4--were transiently up-regulated. The first three were detected at the surface or basement membranes of newly formed myotubes by specific indirect immunofluorescence. Syndecan-3, a satellite cell marker, showed the earliest and most significant increase. Experiments involving myoblast grafting into regenerating muscle showed that C2C12 cell clones, with inhibited Syndecan-3 expression resulting from antisense transfection, presented a normal proliferation rate but an impaired capacity to fuse and form skeletal muscle fibers. These data constitute the first in vivo evidence suggesting the requirement of a specific heparan sulfate proteoglycan for successful skeletal muscle regeneration.

  • Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy.
    Journal of Cellular Biochemistry, 2002
    Co-Authors: Karin Alvarez, Ricardo Fadic, Enrique Brandan
    Abstract:

    Muscular dystrophies are characterized by continuous cycles of degeneration and regeneration that result in extensive fibrosis and a progressive diminution of muscle mass. Cell surface heparan sulfate proteoglycans are found almost ubiquitously on the surface and in the extracellular matrix (ECM) of mammalian cells. These macromolecules interact with a great variety of ligands, including ECM constituents, adhesion molecules, and growth factors. In this study, we evaluated the expression and localization of three heparan sulfate proteoglycans in the biopsies of Duchenne muscular dystrophy (DMD) patients. Through SDS–PAGE analyses followed by specific identification of heparitinase-digested proteins with an anti-Δ-heparan sulfate specific monoclonal antibodies, we observed an increase of three forms of heparan sulfate proteoglycans, corresponding to perlecan, Syndecan-3, and glypican-1. Immunohistochemistry analyses indicated a differential localization for these proteoglycans: glypican-1 and perlecan were found mainly associated to ECM structures, while Syndecan-3 was associated to muscle fibers. These results suggest that the amount of specific heparan sulfate proteoglycans is augmented in skeletal muscle in DMD patients presenting a differential localization. J. Cell. Biochem. 85: 703–713, 2002. © 2002 Wiley-Liss, Inc.

  • Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy.
    Journal of cellular biochemistry, 2002
    Co-Authors: Karin Alvarez, Ricardo Fadic, Enrique Brandan
    Abstract:

    Muscular dystrophies are characterized by continuous cycles of degeneration and regeneration that result in extensive fibrosis and a progressive diminution of muscle mass. Cell surface heparan sulfate proteoglycans are found almost ubiquitously on the surface and in the extracellular matrix (ECM) of mammalian cells. These macromolecules interact with a great variety of ligands, including ECM constituents, adhesion molecules, and growth factors. In this study, we evaluated the expression and localization of three heparan sulfate proteoglycans in the biopsies of Duchenne muscular dystrophy (DMD) patients. Through SDS-PAGE analyses followed by specific identification of heparitinase-digested proteins with an anti-Delta-heparan sulfate specific monoclonal antibodies, we observed an increase of three forms of heparan sulfate proteoglycans, corresponding to perlecan, Syndecan-3, and glypican-1. Immunohistochemistry analyses indicated a differential localization for these proteoglycans: glypican-1 and perlecan were found mainly associated to ECM structures, while Syndecan-3 was associated to muscle fibers. These results suggest that the amount of specific heparan sulfate proteoglycans is augmented in skeletal muscle in DMD patients presenting a differential localization.

  • Antisense inhibition of Syndecan-3 expression during skeletal muscle differentiation accelerates myogenesis through a basic fibroblast growth factor-dependent mechanism.
    Journal of Biological Chemistry, 1999
    Co-Authors: Luis Fuentealba, David J. Carey, Enrique Brandan
    Abstract:

    Abstract Syndecan-3 is a member of a family of transmembrane proteoglycans that posses highly homologous cytoplasmic and transmembrane domains and function as extracellular matrix receptors and low-affinity receptors for signaling molecules such as basic fibroblasts growth factor (FGF-2). Syndecan-3 is transiently expressed in developing limb bud and absent in adult skeletal muscle. In this study we investigated the expression of Syndecan-3 and its role on FGF-2-dependent inhibition of myogenesis. Syndecan-3 expression was down-regulated during skeletal muscle differentiation of C2C12 myoblasts, as determined by Northern blot analyses and immunoprecipitation. To probe the function of Syndecan-3 during myogenesis, C2C12myoblasts were stably transfected with a plasmid coding for antisense Syndecan-3 mRNA. The resulting inhibition of Syndecan-3 expression caused accelerated skeletal muscle differentiation, as determined by expression of creatine kinase and myosin and myoblast fusion. Expression of a master transcription factor for muscle differentiation, myogenin, was also accelerated in antisense Syndecan-3-transfected myoblasts compared with control transfected and wild type cells. Reduced expression of Syndecan-3 resulted in a 13-fold decrease in sensitivity to FGF-2-dependent inhibition of myogenin expression. Addition of heparin partially reversed this effect. These results demonstrate that Syndecan-3 expression is down-regulated during differentiation and the level of expression of membrane-bound heparan sulfate on myoblast surface is critical for fine modulation of responsiveness to FGF-2. These findings strongly suggest a role for Syndecan-3 in regulation of skeletal muscle terminal differentiation.

Guido David - One of the best experts on this subject based on the ideXlab platform.

  • Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation.
    Immunobiology, 2008
    Co-Authors: Lot De Witte, Guido David, Younes Zoughlami, Birgit Aengeneyndt, Yvette Van Kooyk, Lutz Gissmann, Teunis B H Geijtenbeek
    Abstract:

    Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DCs determines the immune response. However, little is known about the receptors on mucosal DC subsets involved in HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV-L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and LCs. We did not observe an involvement for C-type lectins such as dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP binding to DCs was mediated through heparan sulfates, since it was abrogated by heparinase-II treatment. The heparan sulfate proteoglycan Syndecan-3 binds VLPs and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs, strongly correlated with the levels of heparan sulfates and Syndecan-3, suggesting that Syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP interaction with DCs resulted in the up-regulation of co-stimulatory molecules and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results support an important role for Syndecan-3 as a HPV receptor on DCs, which could be important for both vaccine development and understanding HPV pathogenesis.

  • Syndecan 3 is a dendritic cell specific attachment receptor for hiv 1
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Lot De Witte, Guido David, Michael Bobardt, Udayan Chatterji, Gisele Degeest, Teunis B H Geijtenbeek, Philippe Gallay
    Abstract:

    Dendritic cells (DCs) efficiently capture HIV-1 and mediate transmission to T cells, but the underlying molecular mechanism is still being debated. The C-type lectin DC-SIGN is important in HIV-1 transmission by DCs. However, various studies strongly suggest that another HIV-1 receptor on DCs is involved in the capture of HIV-1. Here we have identified Syndecan-3 as a major HIV-1 attachment receptor on DCs. Syndecan-3 is a DC-specific heparan sulfate (HS) proteoglycan that captures HIV-1 through interaction with the HIV-1 envelope glycoprotein gp120. Syndecan-3 stabilizes the captured virus, enhances DC infection in cis, and promotes transmission to T cells. Removal of the HSs from the cell surface by heparinase III or by silencing Syndecan-3 by siRNA partially inhibited HIV-1 transmission by immature DCs, whereas neutralizing both Syndecan-3 and DC-SIGN completely abrogated HIV-1 capture and subsequent transmission. Thus, HIV-1 exploits both Syndecan-3 and DC-SIGN to mediate HIV-1 transmission, and an effective microbicide should target both Syndecan-3 and DC-SIGN on DCs to prevent transmission.

  • Induction of a CXCL8 binding site on endothelial Syndecan‐3 in rheumatoid synovium
    Arthritis & Rheumatism, 2005
    Co-Authors: Angela M. Patterson, Guido David, Lucy Gardner, Jennifer Shaw, Emilie Loreau, Luc Aguilar, Brian A. Ashton, Jim Middleton
    Abstract:

    Objective To identify and characterize which endothelial heparan sulfate proteoglycans (HSPGs) bind the chemokine CXCL8 (interleukin-8) in human rheumatoid arthritis (RA) and nonrheumatoid synovia. Method CXCL8 binding to endothelial HSPGs in RA and nonrheumatoid synovia was determined by heparinase treatment followed by an in situ binding assay and autoradiography. Endothelial HSPGs were characterized by immunohistochemical analysis and quantitative reverse transcriptase–polymerase chain reaction (RT-PCR). Phosphatidyinositol-specific phospholipase C (PI-PLC) and antibodies to HSPGs were used in in situ binding experiments to identify which HSPGs bound CXCL8. Results The expression of heparan sulfate on microvascular endothelial cells was demonstrated in RA and nonrheumatoid synovia. Using antibodies to Syndecan-1–4 and glypican-1, -3, and -4, the selective expression of Syndecan-3 by endothelial cells was detected in RA and nonrheumatoid synovia. In addition, RT-PCR showed the presence of Syndecan-3 messenger RNA in endothelial cells extracted from RA and nonrheumatoid synovia. 125I-CXCL8 bound to venular endothelial cells; treatment with heparinases I and III significantly reduced this binding in RA but not nonrheumatoid synovia. 125I-CXCL8 binding was not reduced after treatment with PI-PLC, which cleaves glycosyl phosphatidylinositol linkages, suggesting that CXCL8 did not bind to glypicans. Treatment of synovia with a Syndecan-3 antibody reduced CXCL8 binding to RA but not nonrheumatoid endothelial cells; however, no reduction in binding was observed with Syndecan-2 or glypican-4 antibodies. Conclusion Our results show the selective induction of a CXCL8 binding site on endothelial Syndecan-3 in RA synovium. This site may be involved in leukocyte trafficking into RA synovial tissue.

  • induction of a cxcl8 binding site on endothelial Syndecan 3 in rheumatoid synovium
    Arthritis & Rheumatism, 2005
    Co-Authors: Angela M. Patterson, Guido David, Lucy Gardner, Jennifer Shaw, Emilie Loreau, Luc Aguilar, Brian A. Ashton, Jim Middleton
    Abstract:

    Objective To identify and characterize which endothelial heparan sulfate proteoglycans (HSPGs) bind the chemokine CXCL8 (interleukin-8) in human rheumatoid arthritis (RA) and nonrheumatoid synovia. Method CXCL8 binding to endothelial HSPGs in RA and nonrheumatoid synovia was determined by heparinase treatment followed by an in situ binding assay and autoradiography. Endothelial HSPGs were characterized by immunohistochemical analysis and quantitative reverse transcriptase–polymerase chain reaction (RT-PCR). Phosphatidyinositol-specific phospholipase C (PI-PLC) and antibodies to HSPGs were used in in situ binding experiments to identify which HSPGs bound CXCL8. Results The expression of heparan sulfate on microvascular endothelial cells was demonstrated in RA and nonrheumatoid synovia. Using antibodies to Syndecan-1–4 and glypican-1, -3, and -4, the selective expression of Syndecan-3 by endothelial cells was detected in RA and nonrheumatoid synovia. In addition, RT-PCR showed the presence of Syndecan-3 messenger RNA in endothelial cells extracted from RA and nonrheumatoid synovia. 125I-CXCL8 bound to venular endothelial cells; treatment with heparinases I and III significantly reduced this binding in RA but not nonrheumatoid synovia. 125I-CXCL8 binding was not reduced after treatment with PI-PLC, which cleaves glycosyl phosphatidylinositol linkages, suggesting that CXCL8 did not bind to glypicans. Treatment of synovia with a Syndecan-3 antibody reduced CXCL8 binding to RA but not nonrheumatoid endothelial cells; however, no reduction in binding was observed with Syndecan-2 or glypican-4 antibodies. Conclusion Our results show the selective induction of a CXCL8 binding site on endothelial Syndecan-3 in RA synovium. This site may be involved in leukocyte trafficking into RA synovial tissue.

  • Distribution of Syndecans 1-4 within the anterior segment of the human eye: expression of a variant Syndecan-3 and matrix-associated Syndecan-2
    Experimental Eye Research, 2004
    Co-Authors: Mark S Filla, Guido David, Robert N. Weinreb, Paul L. Kaufman, Donna M. Peters
    Abstract:

    Control of the actomyosin network plays a role in regulating the movement of aqueous humor through the anterior segment of the eye. Receptors that could control its activity are unknown. In this study, we show that all four members of the Syndecan family, which can regulate the actomyosin network, are present within the anterior segment. In both sections of human anterior segments and cultures of human trabecular meshwork (HTM), Schlemm's canal (HSC) and the ciliary muscle (HCM) cells from the anterior segment, Syndecans-3 and -4 were the predominant family members. They were widely distributed throughout the anterior segment. Syndecan-3 within the anterior segment was a novel, recently described variant 55 kDa form. Low levels of Syndecans-1 and -2 were also observed in situ and in all three cultures. Their expression was weaker and more localized than that observed for Syndecans-3 and -4. Staining for Syndecan-1 in HCM cultures was variable. In HTM and HSC cultures, Syndecan-2 also co-distributed with fibronectin, laminin and type IV collagen suggesting that it was shed and associated with the extracellular matrix. Western blots supported this idea and showed Syndecan-2 ectodomains in lysates from anterior segments.

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