Fuertes, M. B. et al. Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase. Mol. Cell. Biochem. 267, 177-185

Division of Immunogenetics, Hospital de Clínicas José de San Martín, Department of Microbiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Molecular and Cellular Biochemistry (Impact Factor: 2.39). 01/2005; 267(1-2):177-85. DOI: 10.1023/B:MCBI.0000049376.50242.7f
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Recent evidence has implicated galectins and their carbohydrate ligands as novel regulators of T-cell homeostasis. Galectin-1 (Gal-1), a member of this family, inhibits clonal expansion, induces apoptosis of antigen-primed T lymphocytes and suppresses the development of T-cell-mediated autoimmune diseases in vivo. Because the beta-galactoside-binding protein is expressed in activated but not resting T cells, it has been hypothesized that Gal-1-induced apoptosis may constitute an autocrine suicide mechanism to eliminate activated T cells contributing to the termination of an effector immune response. We undertook this study to investigate the signals and intracellular pathways leading to Gal-1 expression during T-cell activation. When T cells were stimulated either with anti-CD3 or anti-CD28 monoclonal antibody plus PMA in the presence of accessory cells, a sustained up-regulation of Gal-1 was observed, reaching a plateau between days 3 and 5 following CD3 engagement or costimulation through CD28. Investigation of the signal transduction events involved in this process revealed a role for Lck and Fyn kinases, since the Src kinase inhibitor PP1 inhibited the up-regulated expression of Gal-1 following T-cell activation. Downstream signaling routes involve mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK) and p38 MAPK, as Gal-1 expression was prevented by U0126 and SB202190. In addition, expression of Gal-1 involves interleukin (IL)-2-dependent signaling routes triggered by p70S6 kinase, as it could be inhibited by rapamycin. This is the first demonstration of the intracellular pathways that control activation-induced expression of Gal-1, which may reveal potential targets for immune intervention to modulate expression of this beta-galactoside-binding protein in pathological disorders.

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    • "It has been shown that the expression of galectins is upregulated in the presence of stimulated B-cells where they play a putative role in immune modulation and T-cell control [35]. Likewise immune mediated activation of T-cells is known to lead to an increased expression of galectin-1 [36]. In view of our histopathological control sections we can however exclude higher concentrations of lymphatic tissue invasion. "
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    ABSTRACT: Galectins are known to regulate cell differentiation and growth as well as cell adhesion and apoptosis. Galectins have been discussed as possible prognosticators for survival in renal cell cancer (RCC) and other urological tumors. They might also play an emerging role as possible new marker-proteins for RCC. In this study, we analyzed the expression of galectin-1 and galectin-3 mRNA in order to further investigate their clinical significance in RCC. Tissue samples were obtained from 106 patients undergoing surgery for RCC. The expression of galectin-1 and galectin-3 mRNA in normal kidney and corresponding cancer tissue was analyzed using quantitative real time PCR. Differences in expression levels of paired tissue samples were assessed using paired two-sample tests. Associations of relative mRNA expression levels in tumor tissues with clinical findings were analyzed using univariate logistic regression. The expression of galectin-1 (p < 0.001) and -3 (p < 0.001) mRNA were significantly higher in RCC when compared to the adjacent normal kidney tissue. For clear cell RCC, an association of male gender with higher galectin-1 and galectin-3 mRNA expression (p = 0.054, p = 0.034) was detected. For all RCCs, galectin-1 mRNA expression failed to show a significant association with advanced disease as well as a higher rate of lymph node metastases (p = 0.058, p = 0.059). The mRNA expression of galectin-1 and galectin-3 is significantly increased in RCC cancer tissue. The higher mRNA expression in tumor tissue of male patients raises the question of a functional connection between galectins and the higher prevalence of RCC in men. Associations with advanced disease might lead to new ways of identifying patients at higher risk of recurrent disease and might even facilitate early metastasectomy with curative intent.
    BMC Clinical Pathology 04/2014; 14(1):15. DOI:10.1186/1472-6890-14-15
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    • "After 4 weeks of culture on microgrooved PCL (polycaprolactone), cells showed slower proliferative activity [106], as suggested, for example, by the down-regulation of ribonuclease/angiogenin inhibitor 1 (RNH1) [110], which functions in binding and inactivating RNase I [111]. Similar results were found following examination of the osteogenic NSQ50 nanotopography, with evidence of the involvement of ERK signalling in downstream regulation of ERK-regulated proteins (e.g., in the upregulation of Hsp70 [112], enolase [113], nucleophosmin [114], osteonectin [115], thioredoxin [116], and galectin-1 [117]). Increased levels of ERK-related proteins went hand-in-hand with observations of rapid mineralization on the topography [20], which confirmed the osteogenic nature of the NSQ50 topography at the protein level. "
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    ABSTRACT: Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated) and direct (force-mediated) mechanotransduction are discussed. Data from proteomic research is also outlined in relation to topography-mediated fate determination, as this approach provides insight into the global molecular changes at the level of the functional effectors.
    Journal of Tissue Engineering 08/2010; 2010(1):120623. DOI:10.4061/2010/120623
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    • "A diverse range of biological functions involved in immune and inflammatory responses and tumour development have been reported for galectins over the last decade including roles in cellular adhesion, migration and survival (see Elola et al. 2007, Yang et al. 2008 for recent reviews). Within the immune system, Gal-1 is specifically localised in lymphoid organs (Baum et al. 1995b), T cells (Blaser et al. 1998, Fuertes et al. 2004), activated macrophages (Rabinovich et al. 1998) and endothelial cells (Lotan et al. 1994, Baum et al. 1995b). Furthermore, expression of Gal-1 in endothelial cells can be modulated by several inflammatory agents, supporting its role in inflammatory incidences (Baum et al. 1995b). "
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    ABSTRACT: A new era of research is being devoted to deciphering endogenous mediators and mechanisms that are in place to resolve the inflammatory response. Accruing evidence indicates that galectins fall into this category of immunoregulatory mediators signifying their use as prospective novel anti-inflammatory agents. The focus of this review is to depict the immunoregulatory bioactivities of three members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9. Emphasis is given to the studies investigating the properties of these endogenous lectins. Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being increasingly recognised as molecular targets for innovative drug discovery.
    Journal of Endocrinology 02/2009; 201(2):169-84. DOI:10.1677/JOE-08-0512 · 3.72 Impact Factor
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