Galectin-3-binding protein: A multitask glycoprotein with innate immunity functions in viral and bacterial infections

Loimaranta, Vuokko; Hepojoki, Jussi; Laaksoaho, Olli; Pulliainen, Arto T.

doi:10.1002/jlb.3vmr0118-036r

Cited by 86 publications

(84 citation statements)

References 92 publications

(220 reference statements)

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“…90 K was initially studied from tumor cells 3 and it is relevant in cancer development and progression 31,32 . It also plays regulatory roles in the immune system; data from the literature concerning the role of 90 K in the immune response has indicated that it may have immunosuppressive as well as immunostimulatory functions depending on the biological context, and it may induce or suppress the secretion of cytokines that play roles in inflammation 1 . It is also induced during viral infections leading to IFN and pro-inflammatory response 33 .…”

Section: Discussionmentioning

confidence: 99%

“…90 K has been detected in biological fluids such as blood 1,13,14 , milk 15 , and more recent studies also reported its presence in the CSF 16,17 . In the serum 90 K was found in circulating microparticles, where it was increased for systemic lupus erythematosus and venous thromboembolism patients 18 .…”

mentioning

confidence: 96%

“…In the serum 90 K was found in circulating microparticles, where it was increased for systemic lupus erythematosus and venous thromboembolism patients 18 . 90 K expression was induced in viral infection 1 and deregulation was also found in some cancer types 13,19 . Concerning neurological diseases the information is scarce.…”

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confidence: 98%

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Investigating LGALS3BP/90 K glycoprotein in the cerebrospinal fluid of patients with neurological diseases

Costa

Pronto-Laborinho

Pinto

et al. 2020

Sci Rep

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Galectin-3 binding protein (LGALS3BP or 90 K) is a secreted glycoprotein found in human body fluids. Deregulated levels were observed in cancer and infection and its study in neurological diseases is more recent. Here, we have investigated 90 K from human cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS, n = 35) and other neurological diseases (n = 23). CSF was fractionated by ultrafiltration/size-exclusion chromatography (SEC) and eluted fractions were analysed by complementary techniques including immunoblotting, electron microscopy and nano-liquid chromatography-tandem mass spectrometry. A fraction of 90 K appeared as nanoparticles of irregular shape with heterogeneous dimensions of 15-60 nm that co-eluted with extracellular vesicles in SEC. Median levels of 90 K quantified by ELISA were not different between ALS patients (215.8 ng/ml) and controls (213.3 ng/ml) in contrast with the benchmark biomarker for ALS phosphoneurofilament heavy chain (1750 and 345 pg/ml, respectively). A multiregression model supported age is the only independent predictor of 90 K level in both groups (p < 0.05). Significant correlation was found between 90 K levels and age for the ALS group (r = 0.366, p = 0.031) and for all subjects (r = 0.392, p = 0.003). In conclusion, this study unveils the presence of 90 K-containing nanoparticles in human CSF and opens novel perspectives to further investigate 90 K as potential aging marker. Galectin-3-binding protein (LGALS3BP, also known as Mac-2BP or tumor-associated antigen 90 K) is a secretory protein with 567 amino acid residues 1. It is heavily N-glycosylated with seven glycosylation sites 2. In early studies 90 K was purified from supernatants of tumor cells where it appeared as large molecular mass complexes 3. Purified full-length recombinant glycoprotein from human embryonic kidney cells was found to self-associate into non-covalent oligomers of 1000-1500 kDa that appeared as ring-like structures and other shapes by electron microscopy. Recombinant 90 K also associated with collagens IV, V and VI, fibronectin and nidogen, it mediated cell adhesion and it was present in the extracellular matrix of mouse tissues 4. 90 K was visualized by electron microscopy in nanoparticles of irregular shape found in extracellular vesicle (EV) fractions from tumor cells in culture 5. More recently, asymmetric flow field-flow fractionation revealed novel nanoparticles from supernatants of tumor cells in culture termed exomeres, which contained 90 K 6. Cells from the human body as well as cells in culture release EV to the surroundings. EV include two major groups, exosomes of endosomal origin and microvesicles that derive from the plasma membrane of cells. EV can be found in body fluids, such as blood 7 or CSF 8-11 and constitute promising tools in disease diagnosis 12. In view of EV heterogeneity several isolation techniques have been used including ultracentrifugation and size-exclusion chromatography (SEC) 12 .

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Section: Discussionmentioning

confidence: 99%

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confidence: 96%

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Investigating LGALS3BP/90 K glycoprotein in the cerebrospinal fluid of patients with neurological diseases

Costa

Pronto-Laborinho

Pinto

et al. 2020

Sci Rep

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“…Unsurprisingly, Ctsk, Ifitm3, CD36, Lgals3bp, which are known to be modulated by inflammatory cytokines, were among those reduced in SKO macrophages. [ 14 ] Ctsk is also expressed in significant levels in human breast cancers and has been shown to play an important role in tumor invasiveness. [ 15 ] Similarly, Lgals3bp belongs to the scavenger receptor and its expression is induced during viral and microbial infection as well as the presence of pathogen‐associated molecular pattern, such as poly(I:C), dsRNA, and dsDNA.…”

Section: Figurementioning

confidence: 99%

Global Proteomic Analyses of STING‐Positive and ‐Negative Macrophages Reveal STING and Non‐STING Differentially Regulated Cellular and Molecular Pathways

Aryal

Hedrick

Onyedibe

et al. 2020

Proteomics Clinical Apps

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Purpose: Cyclic guanosine monophosphate-adenosine monophosphate and other bacterial-derived cyclic di-guanosine monophosphate or cyclic di-adenosine monophosphate trigger innate immune responses through binding to stimulator of interferon genes (STING). Thus in chronic infection, such as in periodontitis, immune cells can be exposed to bacterial DNA and/or cyclic dinucleotides, potentially activating STING to cause inflammation. Thus far the cyclic GMP-AMP synthase-STING-TANK-binding kinase 1 pathway has been well characterized but a global perspective of how the presence or lack of STING affect the proteome is lacking. The aim of this study is to identify macrophage proteins that are affected by STING. Experimental Design: Proteins are extracted from a macrophage cell line harboring STING (RAW-Blue ISG) as well as a STING knockout (STING KO) cell line (RAW-Lucia ISG-KO-STING) and global proteomics analyses are performed.Results: Proteins related to kinase and phosphatase signaling, spliceosome, terpenoid backbone biosynthesis, glycosylation, ubiquitination, and phagocytosis are affected by STING knock out. Conclusions and Clinical Relevance: STING pathway in macrophages is related to the regulation of several proteins that are known as potent biomarkers of various cancers and autoimmune diseases. Moreover, the relation between STING and phagocytosis is demonstrated for the first time.Further validation studies will help identify molecules and pathways that may function as diagnostic or therapeutic targets.

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“…Notably, Galectin-3-binding protein (Lgals3bp) is a protein whose expression is mediated by the canonical activation of the activation of the NF-κB signaling pathway, upon TNFα stimulus (Noma et al, 2012). Lgals3b has been previously demonstrated to induce increased secretion of IL-6 in several different cell lines (Loimaranta et al, 2018), and also promote monocyte migration (Sano et al, 2000). Our results show that TNFα not only promotes the release of Lgals3bp in adipocytes, but its secretion levels increase with prolonged TNFα treatment.…”

Section: Chronic Tnfα Treatment Promotes Differential Regulation Of Smentioning

confidence: 99%

Regulators of TNFα Mediated Insulin Resistance Elucidated by Quantitative Proteomics

Mohallem

Aryal

2020

Preprint

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Obesity is a growing epidemic worldwide and is a major risk factor for several chronic diseases, including diabetes, kidney disease, heart disease, and cancer. Obesity often leads to type 2 diabetes mellitus (T2DM, via the increased production of proinflammatory cytokines such as tumor necrosis factor-α (TNFα). Our study combines different proteomic techniques to investigate the changes in the global proteome, secretome and phosphoproteome of adipocytes under chronic inflammation condition, as well as fundamental cross-talks between different cellular pathways regulated by chronic TNFα exposure. Our results show that many key regulator proteins of the canonical and non-canonical NF-κB pathways, such as Nfkb2, and its downstream effectors, including Csf-1 and Lgals3bp, directly involved in leukocyte migration and invasion, were significantly upregulated at the intra and extracellular levels, culminating in the progression of inflammation. Our data provides evidence of several key proteins that play a role in the development of insulin resistance.

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Galectin-3-binding protein: A multitask glycoprotein with innate immunity functions in viral and bacterial infections

Cited by 86 publications

References 92 publications

Investigating LGALS3BP/90 K glycoprotein in the cerebrospinal fluid of patients with neurological diseases

Investigating LGALS3BP/90 K glycoprotein in the cerebrospinal fluid of patients with neurological diseases

Global Proteomic Analyses of STING‐Positive and ‐Negative Macrophages Reveal STING and Non‐STING Differentially Regulated Cellular and Molecular Pathways

Regulators of TNFα Mediated Insulin Resistance Elucidated by Quantitative Proteomics

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