HUVEC Gene Regulation by Histidine-Rich Glycoprotein
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66768 | GEO | 2015/03/12
SECONDARY ACCESSION(S): PRJNA277917
REPOSITORIES: GEO
Similar Datasets
Project description:Histidine-rich glycoprotein (HRG) is a 75 kDa heparin-binding plasma protein which has been implicated in regulation of tumor angiogenesis and growth. To exert some of its biological functions, HRG acts on macrophages.This study was performed to assess changes in gene expression in peritoneal macrophages treated with HRG using oligonucleotide microarrays
2011-12-06 | GSE34164 | GEO
Project description:Histidine-rich glycoprotein (HRG) is a 75 kDa heparin-binding plasma protein which has been implicated in regulation of tumor angiogenesis and growth. To exert some of its biological functions, HRG acts on macrophages.This study was performed to assess changes in gene expression in peritoneal macrophages treated with HRG using oligonucleotide microarrays A total of 8 samples were analyzed. Peritoneal macrophages were pooled from 10 wt C57/BL6 mice and treated with recombinant HRG (1ug/ml) for 6 and 24 hours in duplicates
2011-12-06 | E-GEOD-34164 | biostudies-arrayexpress
Project description:Histidine-rich glycoprotein (HRG) HRG is a liver-produced protein circulating in human plasma serum at high concentrations of around 125 ug/mL. HRG belongs to the family of type-3 cystatins and has been implicated in a plethora of biological processes, albeit its precise function is still not well understood. Human HRG is a highly polymorphic protein, with at least 5 variants with minor allele frequencies (MAF) of more than 10%, variable in populations from different parts of the world. Considering these 5 mutations we can expect already 35 = 243 possible possibly genetic HRG variants in the population. Here, we purified HRG from serum of 44 individual donors and investigated by proteomics the occurrence of different allotypes, each being either homozygote or heterozygote for each of the 5 mutation sites. We observed that some mutational combinations in HRG were highly favored, while others were apparently missing, although they ought to be present based on the stochastic independent assembly of these 5 mutation sites. To further explore this behavior, we extracted data from the 1000 genome project (n ~ 2500 genomes) and assessed the frequency of different HRG mutants in this larger dataset, observing a prevailing agreement with our proteomics data. From all the proteogenomic data we conclude that the 5 different (frequent) mutations sites in HRG are not occurring independently, but some mutational variants at different sites are fully mutually exclusive, whereas other are highly intwined. Specific mutations also affect HRG abundance and its glycosylation. As the levels of HRG have been suggested as a protein biomarker in a variety of biological processes (e.g., aging, COVID-19 severity, severity of bacterial infections), we here conclude that the highly polymorphic nature of the protein needs to be considered in such evaluations, as these mutations affect HRG’s abundance, structure, post-translational modifications, and function.
2023-10-24 | PXD040914 | Pride
Project description:Intravenous thrombolysis (IVT) with recombinate tissue plasminogen activatior (rt-PA) remains the primary approach for the treatment of acute ischemic stroke (AIS). Based on the short half-life of rt-PA, it is speculated that the coagulative/fibrinolytic cascade induced by alteplase administration might have subsequent longer effect on immune modulation. The exact role of Histidine-rich glycoprotein (HRG), which was found elevated following thrombolysis in this study, on affecting the innate immunity and hemorrhagic transformation (HT) following thrombolysis was investigated in this study. RNA sequencing was performed to show different expressed genes under HRG treatment and revealing the potential regulating pathway.
2024-07-13 | GSE247434 | GEO
Project description:Among the different human lymphoma types, some express the soluble protein Histidine-rich glycorprotein (HRG) in CD20+ tumor cells. Normally HRG is expressed by hepatocytes. We were interested in comparing the gene expression patterns in lymphoma expressing HRG or not in marginal zone lymphomas, which was the lymphoma type with the highest prevalence f HRG (37%).
2021-05-25 | GSE151360 | GEO
Project description:Fungi, such as Candida spp., are commonly found on the skin and at mucosal surfaces. Yet, they rarely cause invasive infections in immunocompetent individuals, an observation reflecting the ability of our innate immune system to control potentially invasive microbes found at biological boundaries. Antimicrobial proteins and peptides are becoming increasingly recognized as important effectors of innate immunity. This is illustrated further by the present investigation, demonstrating a novel antifungal role of histidine-rich glycoprotein (HRG), an abundant and multimodular plasma protein. HRG bound to Candida cells, and induced breaks in the cell walls of the organisms. Correspondingly, HRG preferentially lysed ergosterol-containing liposomes but not cholesterol-containing ones, indicating a specificity for fungal versus other types of eukaryotic membranes. Both antifungal and membrane-rupturing activities of HRG were enhanced at low pH, and mapped to the histidine-rich region of the protein. Ex vivo, HRG-containing plasma as well as fibrin clots exerted antifungal effects. In vivo, Hrg(-/-) mice were susceptible to infection by C. albicans, in contrast to wild-type mice, which were highly resistant to infection. The results demonstrate a key and previously unknown antifungal role of HRG in innate immunity.
| S-EPMC2537934 | biostudies-literature
Project description:Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.
| S-EPMC8119687 | biostudies-literature
Project description:Histidine-rich glycoprotein (HRG) is an abundant plasma glycoprotein with three reported N-glycosylation sites, which integrates many biological processes such as antiangiogenic activity, immune complex clearance and pathogen clearance. Importantly, the protein is known to have five genetic variants with minor allele frequencies of more than 10%, meaning these exist with substantial frequency in the human population. Among them, Pro204Ser can induce a new N-glycosylation site at Asn202. Considerable research has been performed into the biological activity of HRG, while research on its glycosylation is rare. To close this knowledge gap, we used C18-based LC-MS/MS to investigate the glycosylation characteristics of HRG from human plasma, recombinant Chinese hamster ovary (CHO) cell lines and recombinant human embryonic kidney (HEK293) cell lines with targeted mutations. Within human plasma endogenous HRG, every N-glycosylation site proved dominant with a sialylated diantennary complex-type glycan. For the recombinant HRGs, on the other hand, glycans showed different antennarities, sialylation and core-fucosylation, as well as the appearance of oligomannose glycans, LacdiNAc and antennary fucosylation. Furthermore, we discovered a previously unreported O-glycosylation site on residues Thr273/Thr274, which showed an approximate 90% glycan occupancy in all HRG types. To investigate the relevance of HRG glycosylation characteristics and its biological function, we set up an assay to study the plasmin cleavage of HRG under various conditions. In doing so, we showed that the sialylation of the new O-glycan, as well as the genotype-dependent N-glycosylation, significantly influenced the plasmin cleavage of HRG.
2024-05-21 | PXD044353 | Pride
Project description:Whole genomes sequencing to determine mutations in histidine overproducers generated with a toxic histidine analog
| PRJEB45772 | ENA
Project description:Angiogenesis is critical for the growth and proliferation of tumors as well as for normal development. We now describe a novel role for histidine-rich glycoprotein (HRGP) in the modulation of angiogenesis. HRGP is a plasma protein that circulates in relatively high concentrations (1.5 microM), but has no known function in vivo. We have shown previously that HRGP binds with high affinity to thrombospondin-1 (TSP-1), a homotrimeric glycoprotein that is a potent inhibitor of angiogenesis. The antiangiogenic activity of TSP-1 is mediated by the binding of properdin-like type I repeats to the receptor CD36. We found that binding of HRGP to TSP-1 was similarly mediated by TSP type I repeats. HRGP colocalized with TSP-1 in the stroma of human breast cancer specimens, and this interaction masked the antiangiogenic epitope of TSP-1. In assays performed in vitro of endothelial cell migration and tube formation, and in vivo corneal angiogenesis assays, HRGP inhibited the antiangiogenic effect of TSP-1. These studies suggest that HRGP can modulate the antiangiogenic activity of TSP-1, and identify a potential mechanism of resistance to the antiangiogenic effect of TSP-1.
| S-EPMC198540 | biostudies-literature