Age-related differences in human skin proteoglycans

Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human ski

Age-related differences in human skin proteoglycans

Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

Versican is a large chondroitin sulphate proteoglycan produced by several tumour cell types, including high-grade glioma. The increased expression of certain versican isoforms in the extracellular matrix (ECM) plays a role in tumour cell growth, adhesion and migration. Transforming growth factor-β2 (TGF-β2) is an important modulator of glioma invasion, partially by remodeling the ECM. However, it is unknown whether it interacts with versican during malignant progression of glioma cells. Here, we analysed the effect of TGF-β2 on the expression of versican isoforms. The expression of versican V0/V1 was upregulated by TGF-β2 detected by quantitative polymerase chain reaction and immunoprecipitation, whereas V2 was not induced. Using time-lapse scratch and spheroid migration assays, we observed that the glioma migration rate is significantly increased by exogenous TGF-β2 and inhibited by TGF-β2-specific antisense oligonucleotides. Interestingly, an antibody specific for the DPEAAE region of glycosaminoglycan-β domain of versican was able to reverse the effect of TGF-β2 on glioma migration in a dose-dependent manner. Taken together, we report here that TGF-β2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1

Versican G3 Promotes Mouse Mammary Tumor Cell Growth, Migration, and Metastasis by Influencing EGF Receptor Signaling

Increased versican expression in breast tumors is predictive of relapse and has negative impact on survival rates. The C-terminal G3 domain of versican influences local and systemic tumor invasiveness in pre-clinical murine models. However, the mechanism(s) by which G3 influences breast tumor growth and metastasis is not well characterized. Here we evaluated the expression of versican in mouse mammary tumor cell lines observing that 4T1 cells expressed highest levels while 66c14 cells expressed low levels. We exogenously expressed a G3 construct in 66c14 cells and analyzed its effects on cell proliferation, migration, cell cycle progression, and EGFR signaling. Experiments in a syngeneic orthotopic animal model demonstrated that G3 promoted tumor growth and systemic metastasis in vivo. Activation of pERK correlated with high levels of G3 expression. In vitro, G3 enhanced breast cancer cell proliferation and migration by up-regulating EGFR signaling, and enhanced cell motility through chemotactic mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. G3 expressing cells demonstrated increased CDK2 and GSK-3β (S9P) expression, which were related to cell growth. The activity of G3 on mouse mammary tumor cell growth, migration and its effect on spontaneous metastasis to bone in an orthotopic model was modulated by up-regulating the EGFR-mediated signaling pathway. Taken together, EGFR-signaling appears to be an important pathway in versican G3-mediated breast cancer tumor invasiveness and metastasis

ARMOR : Architecture modulaire reconfigurable pour le traitement d'un flot continu de données en temps réel

Dans le cadre particulier des applications traitant un flot continu de données en temps réel, le projet ARMOR, a pour objectif de permettre à un utilisateur de définir la configurtation optimale de la machine, parallèle, qui exécutera son application en temps réel et ce, sans avoir à tenit compte des contraintes temporelles et matérielles. Pour ce faire, nous avons développé, une méthodologie de conception fondée sur l'utilisation d'un modèle. formel. permettant d'expliciter le parallelisme. intrinsèque, d'une application en terme de réseau, de module-il communiquant par mesages. Ce modèle, peut ensuite, être mis en correspondance biunivoque avec une architectune qui se caractérise, par une structure récursive combinant le parallèlisme vrai et le pipe-lining. C'est une architecture, modulaire reconfigurable, dans laquelle des modules matériels sont intenconnectés selon une configuration qui se déduit de l'application

Lesion-induced differential expression and cell association of Neurocan, Brevican, Versican V1 and V2 in the mouse dorsal root entry zone

Lack of regeneration in the CNS has been attributed to many causes, including the presence of inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs). However, little is known about the contribution of CSPGs to regeneration failure in vivo, in particular at the dorsal root entry zone (DREZ), a unique CNS region that blocks regeneration of sensory fibers following dorsal root injury without glial scar formation. The goal of the present study was to evaluate the presence, regulation, and cellular identity of the proteoglycans Brevican, Neurocan, Versican V1 and Versican V2 in the DREZ using CSPG-specific antibodies and nucleic acid probes. Brevican and Versican V2 synthesized before the lesion were still present at high levels in the extracellular matrix of the DREZ several weeks after injury. In addition, Brevican was transiently expressed by reactive oligodendrocytes, and by a subset of astrocytes thereafter. Versican V2 mRNA appeared in NG2-positive cells with the morphology of oligodendrocyte precursor cells. Neurocan and Versican V1 levels were low before injury, and appeared in nestin-positive astrocytes and in NG2-positive cells, respectively, following lesion. Versican V1, but not V2, was also transiently increased in the peripheral dorsal root post-lesion. This is the first thorough description of the expression and cell association of individual proteoglycans following dorsal root lesion. It demonstrates that the proteoglycans Brevican, Neurocan, Versican V1, and Versican V2 are abundant in the DREZ at the time regenerating sensory fibers reach the PNS/CNS border and may therefore participate in growth-inhibition in this region

Changes in steroid receptors and proteoglycan expression in the guinea pig prostate stroma during puberty and hormone manipulation

Published in Prostate, 2007; 67 (3):288-300 at www.interscience.wiley.comBackgroundProteoglycans are structural and informational molecules important during embryogenesis and organ maturation. Maturation of the prostate is influenced by androgens and estrogens, but changes in the relative spatiotemporal expression of steroid receptors and proteoglycans during hormonal change are unexplored.MethodsGuinea pig prostate was used to define hormone-induced changes in the expression of androgen (AR) and estrogen (ER(alpha)) receptors, chondroitin sulfate (CS) glycosaminoglycan and core proteins of versican and syndecan-1. Tissue locations of AR, ER(alpha), CS and the proteoglycans versican and syndecan-1 were determined by immunohistochemistry. Cellular content of ER(alpha) and syndecan-1 was assessed visually. Versican, CS56 epitope, and AR were quantified by image analysis.ResultsAR expression within prostate epithelial and stromal cell nuclei decreased following castration and increased following treatment of castrate animals with dihydrotestosterone (DHT). ER(alpha) expression was restricted to prostate stromal cell nuclei and decreased during puberty, and following treatment of castrate animals with DHT. Versican was present in periacinar stroma immediately peripheral to basal epithelial cells, fibromuscular stromal tissue bands surrounding acinar units, and loose fibrovascular connective tissue interspersed between individual acini. Versican and native CS expression decreased (>10-fold) in periacinar stroma during puberty and following administration of DHT to castrated animals. Expression of syndecan-1 was restricted to fibromuscular cells of prostate stroma, and remained constant during puberty and hormone manipulation.ConclusionsER(alpha), versican core protein and CS side chain epitopes are negatively regulated in prostate stromal tissue by DHT, whilst AR levels are positively regulated.Andrew J. Sakko, Carmela Ricciardelli, Keiko Mayne, Maria T. Dours-Zimmermann, Dieter R. Zimmermann, Petra Neufing, Wayne D. Tilley, Villis R. Marshall and David J. Horsfal