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Results for “Syndecans”

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At least 919 records · Page 51Linked to original sources

PubMed2006

R5- and X4-HIV-1 use differentially the endometrial epithelial cells HEC-1A to ensure their own spread: implication for mechanisms of sexual transmission.

The mechanism of viral transmission across the mucosal barrier is poorly understood. Using the endometrial epithelium-derived cell line HEC-1A, we found that the cells are capable of sequestering large numbers of HIV-1 particles but are refractory to cell-free viral infection. The removal of heparan sulfate moieties of cell-surface proteoglycans (HSPG) from the apical pole of HEC-1A accounted for at least 60% of both R5- and X4-HIV-1 attachment, showing their important implication in viral attachment. HEC-1A cells also have the capacity to endocytose a weak proportion of the attached virus and pass it along to underlying cells. Fucose, N-acetylglucosamine and mannosylated-residues inhibited the transcytosis of some virus isolates, suggesting that mannose receptors can be implicated on the both R5- and X4-HIV-1 transcytosis. The inhibition of HIV transcytosis by blocking CCR5 mAb suggests the implication of specific interaction between the viral gp120 and sulfated moiety of syndecans during the transcytosis of mostly R5- and X4-HIV-1. At the basolateral pole of HEC-1A, HSPG sequestered X4- and not R5-HIV-1, highlighting the important role of HEC-1A as an X4 virus reservoir. The cell-free virus particles that have transcytosed could infect activated T cells but with a weaker efficiency than virus that had not transcytosed. The specific stimulation of HEC-1A by R5-HIV-1 increased the release of monocytes/chemokines-attracting chemokines (IL-8 and GR0) and proinflammatory cytokines (TNF-beta and IL-1alpha) that enhanced the production of virus by activated T cells. This study suggests that R5 and X4 viruses can differentially use epithelial cells to ensure their own spread.

Acetylglucosamine↗

PubMed2005

Src tyrosine kinase-dependent migratory effects of antithrombin in leukocytes.

Tyrosine kinases are known to play a critical role in the regulation of leukocyte function. Antithrombin mediates its effects via syndecan-4 which is known to be linked to the Src tyrosine kinases. In this study, we investigated the role of Src tyrosine kinases in antithrombin-regulated leukocyte migration and Src tyrosine kinase phosphorylation in response to stimulation with antithrombin. Neutrophils and monocytes obtained from forearm venous blood were pre-treated by various Src-family selective tyrosine kinase inhibitors with or without antithrombin followed by washing and assessment of their migratory response toward antithrombin, interleukin-8, or RANTES using Boyden microchemotaxis chambers. Activation status of the two major Src tyrosine kinase phosphorylation sides Tyr416 and Tyr527 was tested using Western blot analysis. Dose-dependent reversal of the antithrombin-mediated effects on neutrophil and monocyte migration was induced by the selective Src kinase inhibitors PP1 and PP2. In Western blot analyses, antithrombin increased Tyr416 and decreased Tyr527 phosphorylation of Src tyrosine kinases in a time- and dose-dependent manner. Moreover, co-incubation with antithrombin lowered the level of RANTES-induced Tyr416 phosphorylation. Therefore, Src tyrosine kinases linked to signaling of antithrombin-binding sites on leukocytes may play an important role in modulating effects on cells function.

Antithrombin III↗

PubMed2004

Intracytoplasmic delivery of anionic proteins.

Protein delivery is emerging as an interesting alternative to gene delivery. We have used our experience with transfection to develop a technique for efficient delivery of anionic proteins such as antibodies into the cytoplasm of cells. As for DNA, when complexed with cationic lipids, large amounts of proteins are shown to enter adherent cells via ubiquitously expressed syndecans. However, protein surface area rather than electric charge ratio governs the delivery characteristics. Delivery of anti-beta-actin and anti-alpha-tubulin IgG's leads to fiber depolymerization. Intracellular delivery of an antibody could thus be regarded as another method for interfering with gene activity.

Animals↗

PubMed2000

Reduced heparan sulfate accumulation in enterocytes contributes to protein-losing enteropathy in a congenital disorder of glycosylation.

Intestinal biopsy in a boy with gastroenteritis-induced protein-losing enteropathy (PLE) showed loss of heparan sulfate (HS) and syndecan-1 core protein from the basolateral surface of the enterocytes, which improved after PLE subsided. Isoelectric focusing analysis of serum transferrin indicated a congenital disorder of glycosylation (CDG) and subsequent analysis showed three point mutations in the ALG6 gene encoding an alpha1,3-glucosyltransferase needed for the addition of the first glucose to the dolichol-linked oligosaccharide. The maternal mutation, C998T, causing an A333V substitution, has been shown to cause CDG-Ic, whereas the two paternal mutations, T391C (Y131H) and C924A (S308R) have not previously been reported. The mutations were tested for their ability to rescue faulty N:-linked glycosylation of carboxypeptidase Y in an ALG6-deficient Saccharomyces cerevisiae strain. Normal human ALG6 rescues glycosylation and A333V partially rescues, whereas the combined paternal mutations (Y131H and S308R) are ineffective. Underglycosylation resulting from each of these mutations is much more severe in rapidly dividing yeast. Similarly, incomplete protein glycosylation in the patient is most severe in rapidly dividing enterocytes during gastroenteritis-induced stress. Incomplete N:-linked glycosylation of an HS core protein and/or other biosynthetic enzymes may explain the selective localized loss of HS and PLE.

Biopsy↗

PubMed2000

Identification of syntenin and other TNF-inducible genes in human umbilical arterial endothelial cells by suppression subtractive hybridization.

Endothelial cells play an important regulatory role in inflammatory responses by upregulating various proinflammatory gene products including cytokines and adhesion molecules. A highly potent mediator of this process is tumor necrosis factor-alpha (TNF). In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-inducible genes in human umbilical arterial endothelial cells. Following mRNA isolation of non-stimulated and TNF-stimulated cells, cDNAs of both populations were prepared and subtracted by suppression PCR. Sequencing of the enriched cDNAs identified 12 genes differentially expressed including vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8 and IkappaBalpha, an inhibitor of the transcription factor nuclear factor-kappaB. Interestingly, also syntenin, a PDZ motif-containing protein which binds to the cytoplasmic domain of syndecans, was identified by SSH. Time course studies using RT-PCR analysis confirmed that all genes were differentially expressed and rapidly induced by TNF. Our data reveal that SSH is a powerful technique of high sensitivity for the detection of differential gene expression in primary arterial endothelial cells.

Carrier Proteins↗

PubMed2001

Rat protein tyrosine phosphatase eta physically interacts with the PDZ domains of syntenin.

The tyrosine phosphatase r-PTPeta is able to suppress the malignant phenotype of rat thyroid tumorigenic cell lines. To identify r-PTPeta interacting proteins, a yeast two-hybrid screening was performed and an insert corresponding to the full-length syntenin cDNA was isolated. It encodes a protein containing two PDZ domains that mediates the binding of syntenin to proteins such as syndecan, proTGF-alpha, beta-ephrins and neurofascin. We show that r-PTPeta is able to interact with syntenin also in mammalian cells, and although syntenin is a tyrosine-phosphorylated protein it is not a substrate of r-PTPeta. The integrity of both PDZ domains of syntenin and the carboxy-terminal region of r-PTPeta are required for the interaction between syntenin and r-PTPeta.

Carrier Proteins↗

PubMed2003

Cell adhesion molecule regulation of nucleocytoplasmic trafficking.

Cells undergo processes such as proliferation, differentiation, and survival based upon cues that they receive from their microenvironment. Extracellular matrix adhesion molecules, such as integrins and syndecans, and cell-cell adhesion molecules, including cadherins and Ig superfamily members, convey information about the environment to the cell. It is evident that cell adhesion molecules (CAMs) regulate a variety of signaling events. An emerging theme is that one level of CAM signaling control is through regulated nucleocytoplasmic distribution of molecules that either phosphorylate or co-activate transcription factors. In this manner, CAMs control transcription events that ultimately have a strong impact on cellular processes.

Animals↗

PubMed1993

Corneal and ocular surface histochemistry.

In summary, this review has provided information concerning the application of histochemical and cytochemical procedures used to detail the normal versus pathological cornea and ocular surface. Specifically, histochemical analysis has been used to study protein and peptide degradation in cornea, to analyze stromal non-collagenous and collagenous fibers and associated extracellular matrix. Cytochemistry of the ocular surface has been used to detail the morphology of corneal and conjunctival mucin. Use of small cationic probes as well as lectin-gold binding was advantageous to quantitatively demonstrate that ocular mucin contains sialylated residues and that the number of these residues significantly changes (increases) with age. These data are important in that the degree of sialylation has been shown to correlate with the ability of bacterial organisms to adhere to and infect the immature in contrast to the mature corneal surface. The use of lectin analysis of diseased ocular tissue also has shown that there are specific alterations in glycoconjugates which occur in the diseased versus normal human cornea. Wound healing in cornea is an important problem which has been studied at length using combined histochemical and biochemical approaches. Results support the hypothesis that apical cell surfaces of the leading edge of a migrating sheet differ from those of the normal epithelium. During wound healing, alpha 6 integrin expression by corneal epithelial cells has been demonstrated, but another protein, syndecan was only seen in non-migrating epithelium which had restratified. The association of immunoglobulins with the ocular surface epithelium of the cornea, their change with age and kinetics of appearance also has been demonstrated using a cytochemical approach. Histochemical procedures have been used to localize Class I and Class II molecules in cornea and conjunctiva. Class II antigen expression has been shown to be absent on corneal endothelium, but it can be induced by treatment with IFN-gamma. These data are of importance in corneal pathology such as that resulting in rejection of corneal transplants. Langerhans cells (Class II, Ia positive) also are not found in normal central cornea. They are localized in the peripheral cornea and are stained histochemically by ADPase, ATPase and by specific anti-Ia and other antisera. Increased numbers of LC have been demonstrated in cornea following various stimuli and in diseases of the cornea including both bacterial and viral induced keratitis.

Aging↗

PubMed2001

Thyroid hormone deficiency alters extracellular matrix protein expression in rat brain.

The effects of thyroid hormone (T3) deficiency on extracellular matrix protein expression were analyzed in newborn rat brain. In hypothyroid animals, a marked increase in the expression of 62 kDa protein was observed in cerebral hemispheres and midbrain, while the 51.6 kDa protein was increased in cerebral hemispheres and decreased in midbrain and the 44.5 kDa protein was down regulated in both structures. On the basis of molecular weights, these proteins may be the proteoglycans cerebroglycan, glypican and N-Syndecan, respectively. In addition, hypothyroidism reduced fibronectin expression in midbrain (-59,7%), but not in cerebral hemispheres. T3 deficiency affects differently the expression of proteins in different brain regions. This may be involved in brain impairment caused by hypothyroidism.

Animals↗

PubMed1994

Regulation of proteoglycan expression in fibrotic liver and cultured fat-storing cells.

Considerable progress has been made in recent years with the molecular dissection of proteoglycans in normal and fibrotic human and rat liver. Proteoglycans constitute a major fraction of extracellular, pericellular and intracellular glycoconjugates. In former times, proteoglycans were classified nearly exclusively on the basis of the composition of their carbohydrate chain (glycosaminoglycan, GAG) attached to the core protein. Accordingly, three main types are discerned in liver, which are in order of decreasing concentrations heparan sulfate (HS, more than 60% of total GAG), dermatan sulfate and chondroitin-4,6-sulfate isomers. Keratan sulfate has not been detected in rat and human liver. Recently, proteoglycans have been characterized by sequencing and cloning of the core proteins to which a number of specific glycosaminoglycan side chains are covalently linked. Accordingly, decorin and biglycan have been identified as major chondroitin sulfate/dermatan sulfate proteoglycans in the extracellular space. In addition, evidence was obtained recently for the expression of aggrecan and lumican, both keratan sulfate bearing proteoglycans, and of syndecan in liver. Using in situ hybridization techniques the temporal and spatial pattern of expression of biglycan, decorin and aggrecan has been assessed. These studies together with Northern blot hybridizations performed with isolated parenchymal and nonparenchymal liver cells confirm that fat-storing cells (Ito cells, perisinusoidal lipocytes), are the most important, principal cellular site of proteoglycan production in diseased liver. The level of expression is regulated by a number of cytokines among which TGF beta, TNF alpha and TGF alpha play significant roles. The effects of these cytokines on proteoglycan expression are dependent on the stage of phenotypic transition of fat storing cells to the activated myofibroblast. Taken together, these data point to the potentially significant role which proteoglycans might fulfil in the regulation of cellular functions and in the maintenance of the supramolecular organization of the extracellular matrix in normal and in diseased liver during the process of fibrogenesis.

Adipocytes↗

PubMed2001

[Structure and regulation of articular cartilage proteoglycan expression].

Beyond aggrecan, the major proteoglycan present in articular cartilage that confers resistance to compressive load and viscoelasticity to the tissue, other proteoglycan families have been described in cartilage. Among them, decorin, biglycan and fibromodulin which belong to the small leucine-rich proteoglycans family bind to matrix components, specially to collagen fibrils and thus regulate fibrillogenesis in cartilage and matrix integrity. These small proteoglycans can also interact with TGF-beta and modulate its bioavailability and stability. The third family is composed by cell surface proteoglycans as syndecans, glypican-1 and betaglycan. These molecules interact with various components of cell environment (growth factors, proteases, matrix components, etc.) and mediate numerous cell functions. Some modifications of one of these proteoglycan expression occur during degenerative pathologies and may lead to alteration of the functional properties of the tissue as well as variations in growth factor bioavailability. These factors are involved in the attempt of cartilage repair initiated by chondrocytes in the early stages of osteoarthritis.

Aggrecans↗

PubMed2003

Spontaneous increase of plasma-like cells with high GANP expression in the extrafollicular region of lymphoid organs of autoimmune-prone mice.

Autoimmune-prone mice bear a hyper-active B cell population generated spontaneously in peripheral lymphoid organs. Expression of beta RNA-primase GANP was shown to be an activation marker in lymphoid follicle germinal center (GC) B cells after immunization with T cell-dependent antigen (TD-Ag) in normal mice. In this study, we examined the expression of GANP in lymphoid tissues of autoimmune-prone mice. GANP expression was up-regulated in GC-B cells after stimulation with TD-Ags; however, highly GANP-positive (GANP(hi)) cells were also observed in lymph nodes of non-immunized MRL/lpr mice. GANP(hi)cells in lymph nodes as well as in spleens of the different autoimmune-prone strains, MRL/lpr, NZB, (NZBxNZW)F1 and BXSB, gradually increased with age. This population was detected only in small numbers in the red pulp region of the spleen after immunization with TD-Ag in normal C57BL/6 and BALB/c mice. GANP(hi)cells had a B220(-)IgM(+)Syndecan-1(+)phenotype, but were negative for PAS-staining and bromo-deoxyuridine incorporation. These results demonstrate that GANP(hi)plasma-like cells appear in lymph nodes of autoimmune mice during aging, suggesting that the new plasma cell population might be generated after hyper-activation of B cells during the course of autoimmune disease.

Animals↗

PubMed2000

Transgenically ectopic expression of Bmp4 to the Msx1 mutant dental mesenchyme restores downstream gene expression but represses Shh and Bmp2 in the enamel knot of wild type tooth germ.

Bmp4 is a downstream gene of Msx1 in early mouse tooth development. In this study, we introduced the Msx1-Bmp4 transgenic allele to the Msx1 mutants in which tooth development is arrested at the bud stage in an effort of rescuing Msx1 mutant tooth phenotype in vivo. Ectopic expression of a Bmp4 transgene driven by the mouse Msx1promoter in the dental mesenchyme restored the expression of Lef-1 and Dlx2 but neither Fgf3 nor syndecan-1 in the Msx1 mutant molar tooth germ. The mutant phenotype of molar but not incisor could be partially rescued to progress to the cap stage. The Msx1-Bmp4 transgene was also able to rescue the alveolar processes and the neonatal lethality of the Msx1 mutants. In contrast, overexpression of Bmp4 in the wild type molar mesenchyme down-regulated Shh and Bmp2 expression in the enamel knot, the putative signaling center for tooth patterning, but did not produce a tooth phenotype. These results indicate that Bmp4 can bypass Msx1 function to partially rescue molar tooth development in vivo, and to support alveolar process formation. Expression of Shh and Bmp2 in the enamel knot may not represent critical signals for tooth patterning.

Alleles↗

PubMed2003

An extracellular matrix-specific microarray allowed the identification of target genes downstream of discoidin domain receptors.

The two discoidin domain receptors, DDR1 and DDR2, are tyrosine kinases that are activated by collagen and are essential regulators of cell-matrix communication. However, the target genes downstream of activated DDRs and their physiological significance are largely unknown. Here, we describe a novel method to dissect signaling pathways induced by extracellular matrix (ECM) receptors. Using the doxycycline-inducible repression system (tet-off), we generated human fibrosarcoma and mouse fibroblast cell lines over-expressing DDR1 or DDR2. These cell lines were employed for gene expression analysis using microarrays specific for human and mouse genes coding for ECM proteins or ECM-interacting factors. We found that approximately 10% of the genes studied were up- or down-regulated more than twofold in response to signals generated by over-expressing DDRs. A common event downstream of DDR1 and DDR2 in human and mouse cells was the up-regulation of P-selectin glycoprotein ligand. Key target genes repressed upon DDR activation were agrin, syndecan-1 and alpha3 integrin. ECM-specific microarrays were found a valuable tool to dissect gene expression changes induced by collagen-receptor signaling pathways.

Animals↗

PubMed1998

Collagenase-1, stromelysin-1 and 92 kDa gelatinase are associated with tumor necrosis factor-alpha induced morphological change of human endothelial cells in vitro.

Recently, we have shown that the tumor necrosis factor-alpha (TNF-alpha)-induced morphological change of EA.hy 926 human endothelial cells is associated with a decrease in the net synthesis of two proteoglycans (PGs), biglycan and syndecan-1, both of which have been suggested to play a role in cell adhesion. Here we have examined whether this phenotypic modulation of EA.hy 926 cells also involves altered expression of matrix metalloproteinases (MMPs) or their tissue inhibitors (TIMPs). We demonstrate that, when forming cobblestone-like monolayer cultures, these cells express and synthesize collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and 72 kDa (MMP-2) and 92 kDa (MMP-9) gelatinases, all of which have previously been found in either normal or pathological human vascular wall. EA.hy 926 cells also express membrane-typel MMP (MT1-MMP), but not matrilysin (MMP-7) and collagenase-3 (MMP-13). As regards TIMPs, we show that these cells express TIMP-1 and TIMP-2, but not TIMP-3 or TIMP-4. Exposure of the cells to TNF-alpha changed the cell morphology from a polygonal shape into a spindle shape and also increased the mRNA levels of MMP-1, MMP-3 and MMP-9, but slightly decreased the MMP-2 mRNA level. No change at the mRNA level of MT1-MMP was observed. Similarly to unstimulated cultures, no mRNA for MMP-7 or MMP-13 was detected in the TNF-alpha treated cultures. TNF-alpha had no effect on the TIMP-1 and TIMP-2 mRNA levels and did not induce TIMP-3 or TIMP-4 expression. Gelatin zymography and Western blot analysis revealed that the increase observed at the mRNA level of MMP-3 and MMP-9 was similar to that of their net protein level; furthermore, the active form of MMP-1 was induced. Our results indicate that the TNF-alpha-induced morphological change of EA.hy 926 cells is associated not only with specific changes in the expression of PGs by the cells, but also with specific changes in the expression of MMPs.

Cell Line↗

PubMed2003

Synaptic adhesion molecules.

Formation, differentiation and plasticity of synapses, the specialized cell-cell contacts through which neurons communicate, all require interactions between pre- and post-synaptic partners. Several synaptically localized adhesion molecules potentially capable of mediating these interactions have been identified recently. Functional studies suggest roles for some of them in target recognition (e.g. SYG-1 and sidekicks), formation and alignment of synaptic specializations (e.g. SynCAM, neuroligin and neurexin), and regulation of synaptic structure and function (e.g. cadherins and syndecan).

Amino Acid Sequence↗

PubMed2002

Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer.

Understanding the details of the molecular mechanism of tumor dissemination revealed that several proteoglycan species are involved in the process but their role can be described as Janus-faced. One level of proteoglycan alterations is at the expression of their genes coding for the core protein. Characteristically, in progressing tumors two patterns emerged: loss or neoexpression of surface proteoglycans (PG) depending on the initial expression pattern of the cell type of origin. The situation is similarly complex concerning the changes of glycosaminoglycan (GAG) of the PG during tumor progression. This is due to the fact that the majority of PGs involved is hybrid molecule meaning that their core protein can be glycanated both with chondroitin and heparan sulfate. However, such an alteration in glycanation of PG may fundamentally change the function of the molecule, especially the one operating at the cell surface. Among the extracellular PGs, decorin emerged as inhibitor of progression while perlecan as a promoter of the process. Analysis of the available data indicate that during metastatization tumor cells must express at least one cell surface HSPG species from the syndecan-glypican-CD44v3 group. Furthermore, the HS-chain of these proteoglycan(s) carry important molecular signatures (suphution or epimerization patterns). Experimental data suggest that tumor cell surface heparan sulfate (PG) may provide a target for specific anti-metastatic interventions.

Animals↗

PubMed2000

Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions.

Heparan sulfate proteoglycans are complex molecules composed of a core protein with covalently attached glycosaminoglycan chains. While the protein part determines localization of the proteoglycan on the cell surfaces or in the extracellular matrix, the glycosaminoglycan component, heparan sulfate, mediates interactions with a variety of extracellular ligands such as growth factors and adhesion molecules. Through these interactions, heparan sulfate proteoglycans participate in many events during cell adhesion, migration, proliferation and differentiation. We are determining the multitude of proteoglycan functions, as their intricate roles in many pathways are revealed. They act as coreceptors for growth factors, participate in signalling during cell adhesion, modulate the activity of a broad range of molecules, and partake in many developmental and pathological processes, including tumorigenesis and wound repair. This review concentrates on biological roles of cell surface heparan sulfate proteoglycans, namely syndecans and glypicans, and outlines the progress achieved during the last decade in unraveling the molecular interactions behind proteoglycan functions.

Animals↗