Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation

Toscano, Marta A.; Allo, Verónica Candela Martínez; Cutine, Anabela María; Rabinovich, Gabriel A.; Mariño, Karina

doi:10.1016/j.molmed.2018.02.008

Cited by 60 publications

(65 citation statements)

References 107 publications

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“…Galectins comprise a family of 15 carbohydrate-binding proteins that via interaction with galactose-containing glycoconjugates regulate pivotal cellular processes like signaling, apoptosis, differentiation, immunity, migration and gene transcription [21][22][23]. The pattern and level of galectins expression varies between cell types and tissues [22,24].…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of fibroblast growth factor receptor 1 trafficking and function by extracellular galectins

et al. 2019

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Fibroblast growth factor receptors (FGFRs) are integral membrane proteins that transmit signals through the plasma membrane. FGFRs signaling needs to be precisely adjusted as aberrant FGFRs function is associated with development of human cancers or severe metabolic diseases. The subcellular localization, trafficking and function of FGFRs rely on the formation of multiprotein complexes. In this study we revealed galectins, lectin family members implicated in cancer development and progression, as novel FGFR1 binding proteins. We demonstrated that galectin-1 and galectin-3 directly bind to the sugar chains of the glycosylated extracellular part of FGFR1. Although both galectins compete for the same binding sites on FGFR1, these proteins elicit different impact on FGFR1 function and cellular trafficking. Galectin-1 mimics fibroblast growth factor as it efficiently activates FGFR1 and receptor-downstream signaling pathways that result in cell proliferation and apoptotic evasion. In contrast, galectin-3 induces extensive clustering of FGFR1 on the cell surface that inhibits constitutive internalization of FGFR1. Our data point on the interplay between extracellular galectins and FGFRs in the regulation of cell fate.

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Section: Introductionmentioning

confidence: 99%

Differential regulation of fibroblast growth factor receptor 1 trafficking and function by extracellular galectins

et al. 2019

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“…These glycan structures are generated by the coordinated action of a set of glycosyltransferases including N-acetylglucosaminyltransferase 5 (MGAT5), an enzyme that creates β 1,6-N-acetylglucosamine-branched complex N-glycans, and core-2 β 1-6-N-acetylglucosaminyltransferase 1 (C2GNT1), an enzyme that catalyzes branching of core-2 O-glycan structures. Conversely, Gal-1 binding is prevented when LacNAc is modified by α 2,6-linked sialic acid incorporated by α 2,6-sialyltransferase 1 (ST6GAL1) [ 3 ]. Gal-1 controls biological processes through extracellular mechanisms by cross-linking cell surface glycoconjugates or intracellularly by influencing a variety of signaling events [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Within the T-cell compartment, Gal-1 promotes apoptosis of CD8 and Th1 and Th17 lymphocytes, promoting a shift toward a Th2-dominant cytokine profile [ 3 , 30 , 31 ]. This effect is highly relevant in cardiovascular diseases as upregulation of Th1 and Th17 cytokines is a typical hallmark observed in patients with acute coronary syndromes [ 32 – 34 ] and is associated with adverse remodeling after AMI [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…Further studies in patients with ischemic as well as nonischemic HF are warranted to better understand the role of Gal-1 in both etiology and prognosis of this disease. Moreover, as different environmental factors may influence Gal-1 expression including hypoxia, inflammation, aging, and metabolic status [ 3 , 17 ], further work is needed to dissect the role of these factors in regulating the activity of this lectin.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, mice lacking Gal-1 showed mild ventricular dilation, reduced contractility, and an enhanced inflammatory infiltrate composed of lymphocytes, macrophages, and NK cells, as well as reduced number of Treg cells, indicative of autoimmune myocarditis ( Table 1 ) [ 19 ]. Moreover, Lgals1 −/− mice showed increased levels of circulating Th1 and Th17 cytokines [ 3 ] which might contribute to ventricular dysfunction and dilation, similar to the dysfunction observed in septic patients [ 46 ], as well as experimental inflammation induced by interleukin- (IL-) 1 β and IL-18 [ 47 , 48 ]. The upregulated expression of Gal-1 in patients with HF may therefore represent a homeostatic mechanism that controls autoimmune myocarditis in response to injury.…”

Section: Introductionmentioning

confidence: 99%

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Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities

Seropián

Gónzalez

Maller

et al. 2018

Mediators of Inflammation

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Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, controls immune cell homeostasis and tempers acute and chronic inflammation by blunting proinflammatory cytokine synthesis, engaging T-cell apoptotic programs, promoting expansion of T regulatory (Treg) cells, and deactivating antigen-presenting cells. In addition, this lectin promotes angiogenesis by co-opting the vascular endothelial growth factor receptor (VEGFR) 2 signaling pathway. Since a coordinated network of immunomodulatory and proangiogenic mediators controls cardiac homeostasis, this lectin has been proposed to play a key hierarchical role in cardiac pathophysiology via glycan-dependent regulation of inflammatory responses. Here, we discuss the emerging roles of Gal-1 in cardiovascular diseases including acute myocardial infarction, heart failure, Chagas cardiomyopathy, pulmonary hypertension, and ischemic stroke, highlighting underlying anti-inflammatory mechanisms and therapeutic opportunities. Whereas Gal-1 administration emerges as a potential novel treatment option in acute myocardial infarction and ischemic stroke, Gal-1 blockade may contribute to attenuate pulmonary arterial hypertension.

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