Cytokine Regulation of Syndecan Expression in Cells of Liver Origin

Sebestyén, Anna; Gallai, Mónika; Knittel, Thomas; Ambrust, Thomas; Ramadori, Giuliano; Kovalszky, Ilona

doi:10.1006/cyto.2000.0754

Cited by 21 publications

(17 citation statements)

References 12 publications

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“…Indeed, while TIARP transcript abundance was strongly induced by TNF␣ in differentiating or fully mature 3T3-L1 cells, undifferentiated 3T3-L1 preadipocytes were unresponsive to the cytokine. Likewise, several target cell-or differentiation-specific actions of TNF␣ have been reported, including effects on preadipocyte and adipocyte (63)(64)(65)(66)(67). This illustrates the requirement of unknown differentiation-dependent mechanisms to activate a permissive response to TNF␣.…”

Section: Discussionmentioning

confidence: 86%

Tumor Necrosis Factor-α-induced Adipose-related Protein (TIARP), a Cell-surface Protein That Is Highly Induced by Tumor Necrosis Factor-α and Adipose Conversion

Moldes

Lasnier

Gauthereau

et al. 2001

Journal of Biological Chemistry

124

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Tumor necrosis factor-␣ (TNF␣) is involved in the physiological and biological abnormalities found in two opposite metabolic situations: cachexia and obesity. In an attempt to identify novel genes and proteins that could mediate the effects of TNF␣ on adipocyte metabolism and development, we have used a differential display technique comparing 3T3-L1 cells exposed or not to the cytokine. We have isolated a novel adipose cDNA encoding a TNF␣-inducible 470-amino acid protein termed TIARP, with six putative transmembrane regions flanked by a large amino-terminal and a short carboxyl-terminal domain, a structure reminiscent of channel and transporter proteins. Commitment into the differentiation process is required for cytokine responsiveness. The differentiation process per se is accompanied by a sharp emergence of TIARP mRNA transcripts, in parallel with the expression of the protein at the plasma membrane. Transcripts are present at high levels in white and brown adipose tissues, and are also detectable in liver, kidney, heart, and skeletal muscle. Whereas the biological function of TIARP is presently unknown, its pattern of expression during adipose conversion and in response to TNF␣ exposure as a transmembrane protein mainly located at the cell surface suggest that TIARP might participate in adipocyte development and metabolism and mediate some TNF␣ effects on the fat cell as a channel or a transporter. Tumor necrosis factor-alpha (TNF␣)1 exerts a wide range of effects on cells and tissues. In addition to its immunological functions, TNF␣ also markedly alters adipose tissue development and metabolism. Surprisingly, TNF␣ seems to be involved in the pathophysiology of two opposite metabolic disorders (1). High plasma levels of TNF␣ likely play an important role in the onset of cachectic states observed during cancer or severe infectious diseases (2). By contrast, more recent studies have indicated that the cytokine is overexpressed in adipose tissue of obese rodents or humans, and that this locally produced TNF␣ may be involved in the obesity-linked insulin resistance (3). Thus, since abnormalities in its production or action are associated with alterations in body fat mass, TNF␣ is likely an important effector of adipose tissue development and metabolism in vivo.Many in vitro studies also support the view that TNF␣ has profound effects on lipid metabolism and adipocyte differentiation. TNF␣ was reported to inhibit lipid storage by reducing synthesis and activity of several proteins essential for lipogenesis, such as lipoprotein lipase (4) and acetyl-coenzyme A carboxylase (5), or by inhibition in the expression and/or function of the insulin-sensitive glucose transporter GLUT4 pathway (6). Otherwise TNF␣ is able to stimulate lipolysis in adipocytes by different mechanisms (7,8). In addition to the above effects on lipid storage or mobilization, TNF␣ potently inhibits adipose conversion and even causes a dramatic de-differentiation of adipocytes in culture (9). Prevention of adipose conversion by TNF␣ has been es...

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Section: Discussionmentioning

confidence: 86%

Tumor Necrosis Factor-α-induced Adipose-related Protein (TIARP), a Cell-surface Protein That Is Highly Induced by Tumor Necrosis Factor-α and Adipose Conversion

Moldes

Lasnier

Gauthereau

et al. 2001

Journal of Biological Chemistry

124

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“…How such effects are mediated is not clear but may be due to the high growth factor binding potential of syndecan-1 (3), which subsequently impacts on IL-6 expression. In breast cancer cells, downregulation of syndecan-1 also results in reduced cellular responses to IL-6 (8), whereas IL-6 downregulates syndecan-1 in a variety of cell types, including cells of liver origin (50), osteosarcoma cell lines (51), and B lymphoid cells (52), suggesting an interdependency between syndecan-1 and IL-6 regulatory pathways.…”

Section: Discussionmentioning

confidence: 99%

Syndecan-1, a Cell Surface Proteoglycan, Negatively Regulates Initial Leukocyte Recruitment to the Brain across the Choroid Plexus in Murine Experimental Autoimmune Encephalomyelitis

Zhang¹,

Wu²,

Song³

et al. 2013

The Journal of Immunology

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The cell surface heparan sulfate proteoglycan, syndecan-1, has been reported to be a negative regulator of various inflammatory processes, but its precise mode of action is poorly defined. In this study, we use the murine model of the 35–55 peptide of myelin oligodendrocyte glycoprotein–induced experimental autoimmune encephalomyelitis (EAE), a T lymphocyte–mediated inflammation where the steps in disease development and recovery are well characterized, to decipher how syndecan-1 impacts on the inflammatory reaction. Syndecan-1 knockout (Sdc-1−/−) mice show enhanced disease severity and impaired recovery. The use of bone marrow chimeric mice reveals that both an immune cell and a CNS-resident source of syndecan-1 contribute to this phenotype. Epithelial cells of the choroid plexus, where initial CCL20-induced leukocyte recruitment to the brain occurs, are identified as the predominant site of syndecan-1 expression. Syndecan-1 is lost from this site during the course of EAE by shedding into the cerebrospinal fluid, which correlates with loss of epithelial cell surface–bound CCL20 and is associated with the upregulation of IL-6 expression. In Sdc-1−/− mice, early leukocyte recruitment via the choroid plexus is enhanced, and IL-6 is elevated, which collectively results in higher numbers of the disease inducing Th17 cells in the CNS, thereby contributing to enhanced disease severity. Furthermore, Sdc-1−/− mice have intrinsically elevated plasma cell numbers and higher myelin oligodendrocyte glycoprotein–specific Ab levels during EAE, which we propose contributes to impaired recovery. Our data identify the choroid plexus epithelium as a novel source of IL-6 in EAE and demonstrate that its expression negatively correlates with syndecan-1 expression at this site.

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“…Similar results were obtained with streptozotocin-induced diabetic rats (data not shown). TGF-␤ increases S2 expression in several cell types (28,29). We, therefore, tested whether the increase in S2 was due to TGF-␤, a known mediator of fibrosis (5).…”

Section: Resultsmentioning

confidence: 99%

Syndecan-2 Regulates Transforming Growth Factor-β Signaling

Chen

Klass

Woods

2004

Journal of Biological Chemistry

114

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Transforming growth factor-␤ (TGF-␤) has multiple functions including increasing extracellular matrix deposition in fibrosis. It functions through a complex family of cell surface receptors that mediate downstream signaling. We report here that a transmembrane heparan sulfate proteoglycan, syndecan-2 (S2), can regulate TGF-␤ signaling. S2 protein increased in the renal interstitium in diabetes and regulated TGF-␤-mediated increased matrix deposition in vitro. Transfection of renal papillary fibroblasts with S2 or a S2 construct that has a truncated cytoplasmic domain (S2⌬S) promoted TGF-␤ binding and S2 core protein ectodomain directly bound TGF-␤. Transfection with S2 increased the amounts of type I and type II TGF-␤ receptors (T␤RI and T␤RII), whereas S2⌬S was much less effective. In contrast, S2⌬S dramatically increased the level of type III TGF-␤ receptor (T␤RIII), betaglycan, whereas S2 resulted in a decrease. Syndecan-2 specifically co-immunoprecipitated with betaglycan but not with T␤RI or T␤RII. This is a novel mechanism of control of TGF-␤ action that may be important in fibrosis.

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Cytokine Regulation of Syndecan Expression in Cells of Liver Origin

Cited by 21 publications

References 12 publications

Tumor Necrosis Factor-α-induced Adipose-related Protein (TIARP), a Cell-surface Protein That Is Highly Induced by Tumor Necrosis Factor-α and Adipose Conversion

Tumor Necrosis Factor-α-induced Adipose-related Protein (TIARP), a Cell-surface Protein That Is Highly Induced by Tumor Necrosis Factor-α and Adipose Conversion

Syndecan-1, a Cell Surface Proteoglycan, Negatively Regulates Initial Leukocyte Recruitment to the Brain across the Choroid Plexus in Murine Experimental Autoimmune Encephalomyelitis

Syndecan-2 Regulates Transforming Growth Factor-β Signaling

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