Human xylosyltransferases in health and disease

Götting, Christian; Kühn, Joachim; Kleesiek, Knut

doi:10.1007/s00018-007-7069-z

Cited by 84 publications

(64 citation statements)

References 165 publications

(225 reference statements)

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“…Primary Chondrocyte Cells-Accumulating evidence indicates that XT-I catalyzes a rate-limiting step in PG synthesis pathway and plays a central role in the regulation of the PG synthesis process both in physiological and physiopathological conditions (18,21,26,27). To understand the mechanism of IL-1␤-mediated alteration of PG synthesis in OA disease and particularly the role of XT-I in this process, we investigated the effect of the cytokine on the expression of XT-I gene in human primary chondrocytes.…”

Section: Xt-i Gene Expression Is Regulated By Il-1␤ In Humanmentioning

confidence: 99%

Regulation of Xylosyltransferase I Gene Expression by Interleukin 1β in Human Primary Chondrocyte Cells

Khair

Bourhim

Barré

et al. 2013

Journal of Biological Chemistry

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Background: Xylosyltransferase I plays a critical role in proteoglycan synthesis. Results: IL-1␤ cytokine regulates xylosyltranserase I expression into an early phase of induction and a late phase of repression through AP-1 and Sp3, respectively. Conclusion: AP-1 and Sp3 are key regulators of IL-1␤-mediated modulation of xylosyltransferase I expression. Significance: Sp3 may be a putative target to prevent IL-1␤-mediated inhibition of proteoglycan synthesis during osteoarthritis.

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Section: Xt-i Gene Expression Is Regulated By Il-1␤ In Humanmentioning

confidence: 99%

Regulation of Xylosyltransferase I Gene Expression by Interleukin 1β in Human Primary Chondrocyte Cells

Khair

Bourhim

Barré

et al. 2013

Journal of Biological Chemistry

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“…17 The GAG chain hinders interaction between decorin core protein and TGF-␤, 18 and hence it may be that decorin CS/DS chain synthesis regulates the sequestration/bioavailability of TGF-␤ in the vessel wall. A key question arising is whether the enzymes xylosyltransferase (XT)-I and XT-II 19 involved in the initial and rate-limiting step in CS/DS chain synthesis, are modulated in oxidative stress-induced vascular calcification. Therefore, we aimed to determine whether GAG chain synthesis on decorin plays an important role in Ox-LDLinduced osteogenic differentiation of VSMCs and to establish the downstream signaling pathway involved.…”

mentioning

confidence: 99%

Decorin GAG Synthesis and TGF-β Signaling Mediate Ox-LDL–Induced Mineralization of Human Vascular Smooth Muscle Cells

Yan

Stringer²,

Hamilton³

et al. 2011

ATVB

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Objective-Decorin and oxidized low-density lipoprotein (Ox-LDL) independently induce osteogenic differentiation of vascular smooth muscle cells (VSMCs). We aimed to determine whether decorin glycosaminoglycan (GAG) chain synthesis contributes to Ox-LDL-induced differentiation and calcification of human VSMCs in vitro. Methods and Results-Human VSMCs treated with Ox-LDL to induce oxidative stress showed increased alkaline phosphatase (ALP) activity, accelerated mineralization, and a difference in both decorin GAG chain biosynthesis and CS/DS structure compared with untreated controls. Ox-LDL increased mRNA abundance of both xylosyltransferase (XT)-I, the key enzyme responsible for GAG chain biosynthesis and Msx2, a marker of osteogenic differentiation. Furthermore, downregulation of XT-I expression using small interfering RNA blocked Ox-LDL-induced VSMC mineralization. Adenoviral-mediated overexpression of decorin, but not a mutated unglycanated form, accelerated mineralization of VSMCs, suggesting GAG chain addition on decorin is crucial for the process of differentiation. The decorin-induced VSMC osteogenic differentiation involved activation of the transforming growth factor (TGF)-␤ pathway, because it was attenuated by blocking of TGF-␤ receptor signaling and because decorin overexpression potentiated phosphorylation of the downstream signaling molecule smad2. Conclusion-These

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“…These defects can lead to early embryonic death (69). Similarly, defects in xylosyltransferase, which initiates glycosylation of proteoglycans, can lead to development of diseases such as diabetes, atherosclerosis, cancer, diabetes, Graves disease, and osteoarthritis (71,72).…”

Section: Discussionmentioning

confidence: 99%

A Novel Function of Heparan Sulfate in the Regulation of Cell-Cell Fusion

O’Donnell

Shukla

2009

Journal of Biological Chemistry

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Despite the important contribution of cell-cell fusion in the development and physiology of eukaryotes, little is known about the mechanisms that regulate this process. Our study shows that glycosaminoglycans and more specifically heparan sulfate (HS) expressed on the cell surface and extracellular matrix may act as negative regulator of cell-cell fusion. Using herpes simplex virus type-1 as a tool to enhance cell-cell fusion, we demonstrate that the absence of HS expression on the cell surface results in a significant increase in cell-cell fusion. An identical phenomenon was observed when other viruses or polyethylene glycol was used as fusion enhancer. Cells deficient in HS biosynthesis showed increased activity of two Rho GTPases, RhoA and Cdc42, both of which showed a correlation between increased activity and increased cell-cell fusion. This could serve as a possible explanation as to why HS-deficient cells showed significantly enhanced cell-cell fusion and suggests that HS could regulate fusion via fine tuning of RhoA and Cdc42 activities.Cell-cell fusion is an important physiological process widespread in organisms ranging from yeast to humans (1). It is critical for several biological phenomena including fertilization, placenta formation, skeletal muscle and bone development, tumorigenesis, immune response, and stem cell differentiation (1-9). Defects in cell-cell fusion can lead to serious diseases, such as myotonic dystrophy, centronuclear myopathy, preeclampsia, and osteopetrosis (10 -13). Defects in sperm-egg fusion are a major cause of infertility (5). Cell-cell fusion has also been utilized for therapeutic applications, including the generation of monoclonal antibody-producing hybridomas (14) as well as new agents for cancer immunotherapy (15-17).Because of its critical nature, many studies have looked at the mechanism by which cell-cell fusion occurs. Although it can occur in a variety of different biological processes, many of the fusion events share common characteristics (8). For example, tetraspanin proteins function in gamete-, myoblast-, macrophage-, and virus-mediated fusion events (18 -21). Although many mediators of cell-cell fusion are known, little is known about the fine-tuning mechanisms that may regulate the membrane fusion process.Viruses have been a useful tool for studying cell-cell fusion since the discovery that they could induce the fusion of somatic cells in vitro (22). Enveloped viruses, like herpes simplex virus type-1 (HSV-1), 2 use transmembrane viral proteins to mediate fusion with the host cell during entry and spread (23-25). For HSV-1, fusion occurs after the virus has attached to host cells by binding to heparan sulfate (HS) using glycoproteins gB and gC (26). Fusion of the virus envelope with the plasma membrane requires that an additional glycoprotein, gD, binds to one of its receptors, a process that also requires HSV-1 gB, gH, and gL (27-29). During HSV-1-mediated cell-cell fusion, gB, gD, gH, and gL are expressed on the surface of infected cells, allowing them to...

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Human xylosyltransferases in health and disease

Cited by 84 publications

References 165 publications

Regulation of Xylosyltransferase I Gene Expression by Interleukin 1β in Human Primary Chondrocyte Cells

Regulation of Xylosyltransferase I Gene Expression by Interleukin 1β in Human Primary Chondrocyte Cells

Decorin GAG Synthesis and TGF-β Signaling Mediate Ox-LDL–Induced Mineralization of Human Vascular Smooth Muscle Cells

A Novel Function of Heparan Sulfate in the Regulation of Cell-Cell Fusion

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