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PubMed1997

Serine phosphorylation of syndecan-2 proteoglycan cytoplasmic domain.

Protein kinase C (PKC) is involved in cell-matrix and cell-cell adhesion, and the cytoplasmic domain of syndecan-2 contains two serines (residues 197 and 198) which lie in a consensus sequence for phosphorylation by PKC. Other serine and threonine residues are present but not in a consensus sequence. We investigated phosphorylation of syndecan-2 cytoplasmic domain by PKC, using purified GST-syndecan-2 fusion proteins and synthetic peptides corresponding to regions of the cytoplasmic domain. A synthetic peptide encompassing the entire cytoplasmic domain of syndecan-2 was phosphorylated by PKC with high affinity. Peptide mapping and substitution studies showed that both serines were phosphoacceptors, but each had slightly different affinity, with that of serine-197 being higher than serine-198. The efficiency of phosphorylation was concentration-dependent. At low concentrations, the cytoplasmic domain peptides were monomeric, with 2 mol/mol serine phosphorylation. At higher concentrations, however, the peptides formed dimers, with only 0.5 mol/mol phosphorylation. Concentration-dependent dimerization was not altered by phosphorylation. Phosphorylation is, therefore, dependent on the conformation of syndecan-2 cytoplasmic domain, but does not affect its oligomeric status.

Amino Acid Sequence↗
PubMed1996

Phosphorylation of a membrane-intercalated proteoglycan, syndecan-2, expressed in a stroma-inducing clone from a mouse Lewis lung carcinoma.

We previously reported that a mouse Lewis lung carcinoma-derived stroma-inducing clone, P29, highly expresses a syndecan-like proteoglycan exhibiting specific binding to fibronectin, a major constituent of the interstitial matrix formed by the induced stromal cells, via its heparan sulphate chains [Itano, Oguri, Nakanishi and Okayama (1993) J. Biochem. (Tokyo) 114, 862-873]. On metabolic labelling of the proteoglycan with [32P]Pi, followed by identification of the radiolabelled material using glycanases, almost all the isotope was found to have been incorporated into a core portion of molecular mass 48 kDa, which was generated by digestion with heparan sulphate lyase I plus chondroitin ABC lyase. Immunoblotting of the core protein with a monoclonal antibody, F58-6G12, demonstrated that the proteoglycan was mouse syndecan-2. CsCl-density-gradient centrifugation after mild treatment of liposome-intercalated 32P-labelled syndecan-2 with trypsin resulted in clear separation of the radioactivity into a bottom fraction containing all the glycosaminoglycans (accounting for 40% of the total radioactivity) and a top fraction containing liposome-associated peptides (60%). The former isotope was shown to be linked covalently to both heparan sulphate and chondroitin sulphate chains, probably at their bridge regions. The latter was mostly attributed to phosphoserine, the one and only phosphorylated amino acid released on acid hydrolysis of this proteoglycan, strongly suggesting that the phosphorylation occurs at a specific serine residue(s) in the cytoplasmic domain of the core protein.

Amino Acid Sequence↗
PubMed1993

Spatial and temporal changes in the expression of fibroglycan (syndecan-2) during mouse embryonic development.

Fibroglycan (syndecan-2) is a member of a family of cell surface heparan sulfate proteoglycans that interact with adhesion molecules, growth factors and a variety of other effector systems that support the shaping, maintenance and repair of an organism. To investigate this apparent redundancy of proteoglycans at the cell surface, we have studied the expression of fibroglycan in the mouse embryo and compared this expression with that of syndecan-1. The characterisation of mouse embryo cDNA clones that crosshybridized to human fibroglycan-cDNA predicted that murine and human fibroglycan were highly similar in structure. Consistently, the analysis of transfectant cells, murine cell lines and embryo extracts indicated that the murine proteoglycan reacted specifically with monoclonal antibody 10H4 developed against the human protein. Fibroglycan, as detected by monoclonal antibody 10H4 in sections of embryonic tissues, occurred exclusively on mesenchymal cells that represented the putative precursors of the hard and connective tissue cells. No fibroglycan was detected in epithelia or in muscle cells. Areas where fibroglycan was particularly abundant were sites of high morphogenetic activity where intense cell-cell and cell-matrix interactions are known to occur (e.g. the epithelial-mesenchymal interfaces, the prechondrogenic and preosteogenic mesenchymal condensations). The expression of fibroglycan was weak in the early embryo, culminated during the morphogenetic phase and at the moment of cell lineage differentiation, and persisted in the perichondrium, periosteum and connective tissue cells. Syndecan-1, in contrast, was primarily detected in epithelia, and transiently in some mesenchymal cells, with mesenchymal localisations that did not or only partially overlap with those of fibroglycan. In situ hybridization analyses confirmed these expression patterns at the transcriptional level, identifying mesenchymal cells as the major source of fibroglycan production. These data indicate that the expression of fibroglycan occurs along unique and developmentally regulated patterns, and suggest that fibroglycan and syndecan-1 may have distinctive functions during tissue morphogenesis and differentiation.

Amino Acid Sequence↗
PubMed1995

Protein kinase C phosphorylates two of the four known syndecan cytoplasmic domains in vitro.

The transmembrane heparan sulfate proteoglycans of the syndecan family are implicated to participate in several cellular reactions which are dependent on protein kinase C. We have used an in vitro assay to assess whether any of the Peptides corresponding to the complete cytoplasmic domains of rat syndecans 1 through 4 were used as substrates for the enzyme. The syndecan-2 (fibroglycan) and syndecan-3 (N-syndecan) peptides were both found to be phosphorylated by protein kinase C with Kms of 15 +/- 3 microM and 85 +/- 25 microM, respectively, while the syndecan-1 and -4 peptides were not phosphorylated under the conditions used. The sites of in vitro phosphorylation for syndecans-2 and -3 were localized to ser-197 and ser-339, respectively. Thus, among 13 available sites (serines and threonines) in the four peptides, two were selectively modified by the enzyme. The specificity and the kinetics of the reactions indicate that the cytoplasmic domains of syndecan-2 and -3 are likely to be physiological substrates for protein kinase C.

Amino Acid Sequence↗
PubMed1996

Developmental and FGF-2-mediated regulation of syndecans (1-4) and glypican in oligodendrocytes.

Differentiating cells undergo developmentally regulated changes in cell-cell and cell-matrix adhesion that control migration through microenvironments, proliferation, and differentiation. The diversity of the patterns of expression of heparan sulfate proteoglycans (HSPGs), coupled with their interactions with extracellular matrix, cell adhesion molecules, and growth factors, has emphasized their critical importance in the regulation of these events. Syndecans (1-4), glypican, and cerebroglycan are membrane-associated HSPGs that have been implicated in these events in various tissues and several tumor cell lines. We have examined the developmental expression and FGF-2-mediated regulation of these HSPGs during differentiation within a specific lineage of primary cells, oligodendrocytes (OL). Northern analyses of highly purified, developmentally synchronized populations of OL-lineage cells at three stages of differentiation (early and late progenitors and mature OLs) showed that the expression of individual forms of these syndecans and glypican are developmentally regulated. Specifically, the level of expression of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to postmitotic mature cells. The expression of syndecan-1 and -3 had the inverse developmental pattern. Therefore, these two sets of molecules may have different roles in regulating the onset of terminal differentiation in OLs. The levels of mRNA expression were regulated by FGF-2: in late progenitors, FGF-2 induced a doubling of the mRNA levels of syndecan-2, -3, and -4, while those for syndecan-1 and glypican remained unaffected; in mature OLs, the levels of syndecan-1 mRNA were up-regulated, the levels of syndecan-2 and -4 and glypican were down-regulated. These results suggest that the individual syndecan molecules have distinct functions during the differentiation process and that multiple levels of regulation must exist, leading to a changing repertoire of these molecules during OL lineage progression and myelinogenesis.

Animals↗
PubMed1997

Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3' to the SDC2 gene.

An X;8 translocation was identified in a 27-year-old female patient manifesting multiple exostoses and autism accompanied by mental retardation and epilepsy. Through molecular analysis using yeast artificial chromosomes (YACs) and cosmid clones, the translocation breakpoint was isolated and confirmed to be reciprocal within a 5'-GGCA-3' sequence found on both X and 8 chromosomes without gain or loss of a single nucleotide. The translocation breakpoint on the X chromosome occurred in the first intron of the gastrin-releasing peptide receptor (GRPR) gene and that on chromosome 8 occurred approximately 30 kb distal to the 3' end of the Syndecan-2 gene (SDC2), also known as human heparan sulfate proteoglycan or fibroglycan. The GRPR gene was shown to escape X-inactivation. A dosage effect of the GRPR and a position effect of the SDC2 gene may, however, contribute the phenotype observed in this patient since the orientation of these genes with respect to the translocation was incompatible with the formation of a fusion gene. Investigation of mutations in these two genes in unrelated patients with either autism or multiple exostoses as well as linkage and association studies is needed to validate them as candidate genes.

Adult↗
PubMed1997

Developmental and cell-type-specific expression of cell surface heparan sulfate proteoglycans in the rat heart.

The expression of cell surface heparan sulfate proteoglycans in rat heart was investigated by Northern blot analysis with specific cDNA probes. In adult heart syndecan-3 and glypican mRNAs were abundantly expressed. Lower levels of syndecan-2 mRNA and very low levels of syndecan-1 mRNA were also detected. Analysis of RNA isolated from hearts of rats of various ages revealed that syndecan-3 and glypican mRNAs levels increased dramatically at birth, and continued to be expressed at high levels in adult animals. To determine which of these proteoglycans was expressed in cardiomyocytes, primary cultures of cardiomyocytes and nonmyocytes isolated from neonatal rat hearts were analyzed for proteoglycan expression. Glypican mRNA was localized almost exclusively to cardiomyocytes. Syndecan-3 mRNA was not detected in myocytes, but was detected in the nonmyocyte cells. Biochemical characterization of cardiomyocyte glypican revealed that it was a phosphatidylinositol-anchored heparan sulfate proteoglycan. Results of immunofluorescent staining of rat hearts with anti-glypican antibodies were consistent with the Northern blot data, and localized glypican to the lateral regions of myocyte plasma membrane that contact the basement membrane, as well as sites of myocyte adhesion junctions. At the latter site glypican colocalized with vinculin. Visualization of basic fibroblast growth factor binding sites by means of a tissue slice overlay assay also revealed colocalization with glypican. These results demonstrate developmental and cell-type-specific expression of membrane heparan sulfate proteoglycans in the heart. They also show that glypican is a major heparan sulfate proteoglycan expressed on the cardiomyocyte plasma membrane.

Animals↗
PubMed1994

Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family.

The syndecans are a family of four cell surface heparan sulfate proteoglycans in vertebrates that mediate a variety of cell behaviors, including cell adhesion and the action of growth factors. Their core proteins contain conserved transmembrane and cytoplasmic domains but divergent extracellular regions in which only the glycosaminoglycan attachment sites are conserved. By extensive PCR analyses based on the conserved sequences, we find only four syndecan-related sequences in the mouse. These correspond to the previously described core proteins of syndecan proteoglycans from other vertebrates. We have mapped the genes for syndecan-2 to chromosome 15, syndecan-3 to chromosome 4, and syndecan-4 to chromosome 2 in the mouse. Together with the previous localization of the gene for syndecan-1 to chromosome 12, these data establish that the four syndecan genes are dispersed on different chromosomes and that each syndecan gene is located near a member of the myc gene family. Synd1 is next to Nmyc, Synd2 close to myc, Synd3 near Lmyc, and Synd4 on the same chromosome as Bmyc. The physical relationship between the members of these two gene families appears to be ancient and conserved after the two genome duplications thought to have occurred during vertebrate evolution.

Animals↗
PubMed1996

Gene expression of syndecans and betaglycan in isolated rat liver cells.

Membrane-bound heparan sulfate proteoglycans act as coreceptors for cytokines and are involved in cell-matrix or cell-cell adhesion. We have determined the gene expression of all four members of the syndecan-like integral membrane proteoglycans and of betaglycan, the transforming growth factor-beta type III receptor, in various types of isolated hepatic cells of the rat. Fat-storing cells express syndecan-1, -2, -3, -4, and betaglycan. During the transformation of fat-storing cells into myofibroblasts (the key process in the development of liver cirrhosis), the levels of mRNA for syndecan-1, -3, and -4 remain constant, whereas the amount of syndecan-2 mRNA increases and that for betaglycan decreases. Liver macrophages express syndecan-3 and -4, but only small amounts of syndecan-1. Freshly isolated hepatocytes express only syndecan-1, -2, and -4, but fail to express betaglycan. During cultivation, hepatocytes start to express betaglycan. Syndecan-3, -4, and betaglycan are transcribed into one mRNA population, whereas syndecan-1 and -2 are expressed in different-sized mRNA populations. The data show that the genes of all tested membrane heparan sulfate proteoglycans are expressed by hepatic cells, but that each cell type is characterized by its specific heparan sulfate proteoglycan mRNA profile.

Animals↗
PubMed1996

Heparan sulfate proteoglycan expression in chronic cholestatic human liver diseases.

The mechanism of bile ductular reaction and accompanying fibrogenesis depends on interactions of ductular cells with the matrix and growth factors. Heparan sulfate proteoglycans (HSPGs) are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. We used monoclonal antibodies specific for the cell surface HSPGs (syndecans, glypican), for matrix HSPG (perlecan), and for heparan sulfate carbohydrate (HS) to investigate their immunohistochemical expression in 20 specimens with chronic cholestatic liver disease and in five normal human liver specimens. Because activated hepatic stellate cells (HSC are a major source of fibrosis in the liver, we also examined HSPG expression in primary cultures of human activated HSC using immunocytochemistry and Western blotting and for syndecan-1 also Northern blotting. In comparison with bile ductular cells of normal liver, reactive ductules in chronic cholestasis were marked by an elevated expression of syndecan-1, surrounded by an increased perlecan expression. In acinar zone 1, large stimulated macrophages and HSC, present in increased numbers, were strongly positive for syndecan-3. Cultured HSC showed a membranous staining pattern for syndecan-1, syndecan-3, and heparan sulfate, and in addition intracellular staining for syndecan-2, -3, and 4. Perlecan immunoreactivity was detected as intercellular strings. Western blotting revealed positive bands with all antibodies and Northern blotting for syndecan-1 was also positive. These results show that cultured human HSC can synthesize all four syndecans, glypican, and perlecan. These data reveal changes in the expression of syndecan-1, syndecan-3, and perlecan in human chronic cholestatic liver disease, that may be important in the deposition of matrix components and activation of growth factors that support ductular reaction and accompanying fibrogenesis.

Antibodies, Monoclonal↗
PubMed1996

Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican.

The formation of distinctive basic FGF-heparan sulfate complexes is essential for the binding of bFGF to its cognate receptor. In previous experiments, cell-surface heparan sulfate proteoglycans extracted from human lung fibroblasts could not be shown to promote high affinity binding of bFGF when added to heparan sulfate-deficient cells that express FGF receptor-1 (FGFR1) (Aviezer, D., D. Hecht, M. Safran, M. Eisinger, G. David, and A. Yayon. 1994. Cell 79:1005-1013). In alternative tests to establish whether cell-surface proteoglycans can support the formation of the required complexes, K562 cells were first transfected with the IIIc splice variant of FGFR1 and then transfected with constructs coding for either syndecan-1, syndecan-2, syndecan-4 or glypican, or with an antisense syndecan-4 construct. Cells cotransfected with receptor and proteoglycan showed a two- to three- fold increase in neutral salt-resistant specific 125I-bFGF binding in comparison to cells transfected with only receptor or cells cotransfected with receptor and anti-syndecan-4. Exogenous heparin enhanced the specific binding and affinity cross-linking of 125I-bFGF to FGFR1 in receptor transfectants that were not cotransfected with proteoglycan, but had no effect on this binding and decreased the yield of bFGFR cross-links in cells that were cotransfected with proteoglycan. Receptor-transfectant cells showed a decrease in glycophorin A expression when exposed to bFGF. This suppression was dose-dependent and obtained at significantly lower concentrations of bFGF in proteoglycan-cotransfected cells. Finally, complementary cell-free binding assays indicated that the affinity of 125I-bFGF for an immobilized FGFR1 ectodomain was increased threefold when the syndecan-4 ectodomain was coimmobilized with receptor. Equimolar amounts of soluble syndecan-4 ectodomain, in contrast, had no effect on this binding. We conclude that, at least in K562 cells, syndecans and glypican can support bFGF-FGFR1 interactions and signaling, and that cell-surface association may augment their effectiveness.

Base Sequence↗
PubMed1997

Syndecan-4 is a primary-response gene induced by basic fibroblast growth factor and arterial injury in vascular smooth muscle cells.

Syndecans are a family of transmembrane proteoglycans that have been implicated in cell-extracellular matrix adhesion and growth factor binding. We reported previously that syndecan-1 expression by cultured rate vascular smooth muscle cells (VSMCs) is induced by serum- or platelet-derived growth factor (PDGF). We now report that syndecan-4 mRNA is rapidly induced in cultured VSMCs in response to basic fibroblast growth factor (bFGF) or serum stimulation. In the presence of cycloheximide, induction of syndecan-4 mRNA was enhanced. These characteristics identified syndecan-4 as a primary-response gene product in VSMCs. In contrast, syndecan-1 mRNA expression in response to serum was completely blocked in the presence of cycloheximide. We also examined the expression of syndecan mRNAs in VSMCs in response to balloon catheter injury in vivo. A reverse transcriptase-polymerase chain reaction technique was developed that enabled us to amplify all four syndecan mRNAs in a single reaction tube and determine relative changes in their expression. All four syndecan mRNAs were detected in uninjured rat carotid arteries. In endothelium-denuded arteries, the medial layer (presumably VSMCs) accounted for 70% to 90% of the syndecan mRNAs in the vessel wall. The levels of syndecan-2 and syndecan-3 mRNAs were not altered significantly after balloon injury. In contrast, syndecan-4 mRNA was increased at early times after injury but then decreased to control level by 7 days. Syndecan-1 mRNA levels showed a slower but prolonged increase that reached a maximum at 7 days after injury. Immunostaining with anti-syndecan-4 antibodies demonstrated a rapid increase in syndecan-4 proteoglycan expression in the injured carotid artery.

Animals↗
PubMed1994

Differential expression of multiple cell-surface heparan sulfate proteoglycans during embryonic tooth development.

Heparan sulfate accumulates on cell surfaces and at cell-matrix interfaces, and functionally modulates several of the effector molecules that support the interactions, growth, and differentiation of developing tissues. Using heparin sulfate-specific monoclonal antibodies MAb, we obtained evidence that extracts from rodent embryos contain multiple forms of cell surface-associated heparan sulfate proteoglycan (PG). Taking tooth development in the mouse embryo as a model to further investigate the relevance of this PG redundancy and using MAb against heparan sulfate, antibodies specific for syndecan (syndecan-1) and fibroglycan (syndecan-2) (two distinct members of a larger family of cell-surface heparan sulfate PGs), and specific cDNA probes for these two cell-surface PGs, we obtained in situ evidence for regulated and differential expression of multiple cell-surface heparan sulfate PGs. The unique, distinctive, and coordinated changes in the expressions of these PGs during morphogenesis and differentiation of dental tissues suggest that the various cell-surface PGs are not truly redundant but play important, specific, and potentially complementary roles during embryonic development.

Animals↗
PubMed1996

Embryonic expression patterns of Xenopus syndecans.

Syndecans are a family of heparan sulfate proteoglycans implicated in cell-cell and cell-matrix interactions. To investigate the roles of syndecans in early development, we identified three syndecan family members in Xenopus laevis: Xsyn-1, Xsyn-2, and Xsyn-3. Xsyn-1 and Xsyn-2 are maternal mRNAs localized to the animal pole in blastulae, and are expressed in the ectoderm of gastrulae. In neurulae, Xsyn-1 is restricted to non-neural ectoderm and Xsyn-2 is restricted to neural ectoderm. In tailbud embryos, the three syndecans are expressed in adjacent, non-overlapping patterns. Xsyn-2 is expressed in the heart while Xsyn-1 is expressed in the underlying anterior endoderm. Xsyn-3 is expressed in the hindbrain, midbrain, and forebrain, while Xsyn-2 is expressed in the intervening regions. These results suggest that different members of the syndecan family have distinct developmental roles, perhaps acting as barriers to define tissue boundaries.

Amino Acid Sequence↗
PubMed1995

Expression of a Xenopus counterpart of mammalian syndecan 2 during embryogenesis.

We have identified a Xenopus cDNA, XS-2, by screening a Xenopus embryonic stage-22-24 cDNA library with a DNA probe encoding the transmembrane and cytoplasmic domains of mouse syndecan 1. The 1.4 kb cDNA consists of an open reading frame of 642 nucleotides encoding a protein of 191 amino acids. The predicted protein of 20869 Da contains a 25-amino acid putative transmembrane domain and a 32-amino acid putative cytoplasmic domain, both of which are highly similar to the corresponding regions of rat syndecan 2 (92% identity) and to a lesser degree those of rat syndecans 1, 3 and 4 (62, 64 and 78% respectively). The putative N-terminal ectodomain contains a possible attachment site for heparan sulphate, identical with the comparable glycosaminoglycan-attachment sequence of rat syndecan 2. Polyclonal antisera raised against recombinant ectodomain of XS-2, expressed as a fusion protein, recognized a heparan sulphate proteoglycan in XTC cell-culture medium. This proteoglycan bound to DEAE-Sephacel and was eluted with 1 M NaCl; digestion with heparitinase but not chondroitinase ABC resulted in the identification of a 46 kDa protein by these antisera. Northern-blot analysis indicated that XS-2 identifies two Xenopus mRNA species approx. 4 and 2 kb in size in embryos ranging in maturation from the 64-cell stage to stage 54. These results demonstrate that a heparan sulphate proteoglycan, similar to syndecan 2, is expressed during Xenopus embryogenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Time-dependent increases in syndecan-1 and fibroglycan messenger RNA expression in the infarct zone after experimentally induced myocardial infarction in rats.

BACKGROUND: Syndecan-1 and fibroglycan, heparan sulphate proteoglycans, play important roles in extracellular matrix formation via their biological functions. OBJECTIVE: To examine experimentally the sequential changes in syndecan-1 and fibroglycan messenger RNA (mRNA) expression after acute myocardial infarction. MATERIALS AND METHODS: The left coronary arteries of male Sprague-Dawley rats were ligated and the hearts were excised on days 1-14, 28 and 42. Syndecan-1 and fibroglycan mRNA expression in the infarct and non-infarct zones and in sham-operated hearts was determined by reverse transcriptase-polymerase chain reaction. Amplified products were quantified by densitometry of the electrophoresed bands stained with ethidium bromide and standardized relative to the glyceraldehyde 3-phosphate dehydrogenase or beta-actin mRNA expression. Northern hybridization was also performed in the infarct and non-infarct zones on day 3. RESULTS: Expression both of syndecan-1 and of fibroglycan mRNA began to increase on day 2. The expression attained maximum levels on day 3. The maximum levels of syndecan-1 and fibroglycan expression were, respectively, sevenfold and fivefold the preligation level and the level in the sham-operated hearts. The levels remained elevated until day 14, whereupon they declined gradually, returning to the control levels by around day 42. Northern blotting also demonstrated that there was an increased expression both of syndecan-1 and of fibroglycan mRNA in the infarct compared with that in the non-infarct zone on day 3. CONCLUSION: Our results demonstrated that there are sequential increases in the expression both of syndecan-1 and of fibroglycan mRNA in the infarct zone after experimentally induced myocardial infarction in rats, suggesting that these proteoglycans play some role in the pathological course of infarction.

Animals↗
PubMed1993

Differential expression of transmembrane proteoglycans in vascular smooth muscle cells.

Rat aortic vascular smooth muscle (VSM) cells synthesize the transmembrane proteoglycan syndecan (Cizmeci-Smith, G., Asundi, V., Stahl, R. C., Teichman, L. J., Chernousov, M., Cowan, K., and Carey, D. J. (1992) J. Biol. Chem. 267, 15729-15736). The present work demonstrated that VSM cells synthesize the related transmembrane proteoglycan fibroglycan and that increased expression of these two proteoglycans is stimulated under different conditions. Fibroglycan synthesis by cultured rat aortic VSM cells was demonstrated by Northern blot analysis with a rat fibroglycan cDNA probe and immunoblot analysis with anti-rat fibroglycan antibodies. Effects of growth factors and vasoactive substances on syndecan and fibroglycan expression were examined by Northern blot analysis. Syndecan mRNA levels increased in response to stimulation of VSM cells with serum, platelet-derived growth factor, or angiotensin II. VSM cells stimulated with platelet-derived growth factor contained more syndecan core protein and processed syndecan than control cells. Fibroglycan mRNA levels either decreased or remained unchanged in response to these agents. Fibroglycan mRNA levels increased following transforming growth factor-beta stimulation, while syndecan mRNA levels decreased. Other agents, including basic fibroblast growth factor, endothelin, and carbacyclin did not alter the expression of either proteoglycan. Syndecan and fibroglycan mRNA levels also varied as a function of cell density. These data demonstrate that syndecan and fibroglycan expression are regulated differently in VSM cells and lend support to the hypothesis that these proteoglycans carry out distinct physiological functions.

Angiotensin II↗