Inducible LGALS3BP/90K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex

Xu, Gang; Xia, Zhangchuan; Deng, Fei‐Yan; Liu, Lin; Wang, Qiming; Yu, Yongsheng; Wang, Xinghuan; Zhu, Chengliang; Liu, Weiyong; Cheng, Zhikui; Zhu, Ying; Zhou, Li; Zhang, Yi; Lu, Mengji; Shi, Lei

doi:10.1371/journal.ppat.1008002

Cited by 47 publications

(39 citation statements)

References 38 publications

(41 reference statements)

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“…Gal-3BP is suggested to be a major upstream molecule in the activation of inflammatory factors, including IL-6 and TNF-α, by playing an important role in macrophage polarization and activation. In addition, several investigations have suggested a strong link between Gal-3BP levels and metabolic disorders, consistent with systemic pro-inflammation, by influencing inflammatory signalling pathways, including JNK-STAT and IKKβ/NF-κB [20][21][22][23]. There is solid evidence that insulin resistance is related to inflammation with both the fluctuation of cytokines and the relevant signalling pathways.…”

Section: Discussionmentioning

confidence: 93%

Elevated serum levels of galectin-3 binding protein is associated with insulin resistance in non-diabeteic women after menopause

Chen

Das

Zhuo

et al. 2020

Preprint

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Background Galectin-3 binding protein (GAL-3BP) is one of the major fucosylated glycoprotein family members, and is implicated in nonalcoholic fatty liver disease, lipid dysfunctions and coronary artery disease recently. Here we analyzed the serum concentrations of GAL-3BP in postmenopausal women, to evaluate the association of circulating GAL-3BP and insulin resistance in female after menopause.Method We evaluated serum levels of Gal-3BP in sixty-two non-diabetic women in menopausal status for at least one year. The clinical features, biochemistry profiles and homeostasis model assessment of insulin resistance (HOMA-IR) were obtained routinely.Results Gal-3BP levels increased in women with higher HOMA-IR values and was positively correlated to HOMA-IR. It was also an independent risk factors for HOMA-IR and showed the most influence on HOMA-IR comparing to FPG, TG, age and BMI. The cut-off value of serum Gal-3BP level was 2234.3150 ng/ml with the area under the ROC curve (AUC) 0.68 (HOMA-IR 1.5), 0.81 (HOMA-IR 2.0) and 0.93 (HOMA-IR 2.5).Conclusions Serum levels of Gal-3BP is associated with impaired insulin sensitivity in non-diabetic menopausal women.

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Section: Discussionmentioning

confidence: 93%

Elevated serum levels of galectin-3 binding protein is associated with insulin resistance in non-diabeteic women after menopause

Chen

Das

Zhuo

et al. 2020

Preprint

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“…Both have been confirmed to be expressed in upper airway tissues ( Fink et al, 2013 ; Clifford et al, 2016 ). As for their respective capacities for distinguishing upper airway samples from different subjects under various pathological conditions, LAGLS3BP has a specific expression level following the activation of neutrophil-mediated immune responses, which is generally observed during viral infections ( Andres-Terre et al, 2015 ; Xu et al, 2019 ) including but not restricted to SARS-CoV-2 infection ( Didangelos, 2020 ; Park et al, 2020 ). Therefore, LAGLS3BP may also help in distinguishing samples from disease controls and those from patients with viral infection but not the detailed subgrouping of infections.…”

Section: Discussionmentioning

confidence: 99%

Identifying Transcriptomic Signatures and Rules for SARS-CoV-2 Infection

Zhang

Zeng

et al. 2021

Front. Cell Dev. Biol.

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The world-wide Coronavirus Disease 2019 (COVID-19) pandemic was triggered by the widespread of a new strain of coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Multiple studies on the pathogenesis of SARS-CoV-2 have been conducted immediately after the spread of the disease. However, the molecular pathogenesis of the virus and related diseases has still not been fully revealed. In this study, we attempted to identify new transcriptomic signatures as candidate diagnostic models for clinical testing or as therapeutic targets for vaccine design. Using the recently reported transcriptomics data of upper airway tissue with acute respiratory illnesses, we integrated multiple machine learning methods to identify effective qualitative biomarkers and quantitative rules for the distinction of SARS-CoV-2 infection from other infectious diseases. The transcriptomics data was first analyzed by Boruta so that important features were selected, which were further evaluated by the minimum redundancy maximum relevance method. A feature list was produced. This list was fed into the incremental feature selection, incorporating some classification algorithms, to extract qualitative biomarker genes and construct quantitative rules. Also, an efficient classifier was built to identify patients infected with SARS-COV-2. The findings reported in this study may help in revealing the potential pathogenic mechanisms of COVID-19 and finding new targets for vaccine design.

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“…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 . 90 K was also suggested as potential biomarker in several diseases.…”

Section: Discussionmentioning

confidence: 99%

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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Inducible LGALS3BP/90K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex

Cited by 47 publications

References 38 publications

Elevated serum levels of galectin-3 binding protein is associated with insulin resistance in non-diabeteic women after menopause

Elevated serum levels of galectin-3 binding protein is associated with insulin resistance in non-diabeteic women after menopause

Identifying Transcriptomic Signatures and Rules for SARS-CoV-2 Infection

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

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