ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The clinical value of suPAR in diagnosis and prediction for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.Therapeutic advances in respiratory diseasePooled it
- Comparative analyses of monocyte memory dynamics from mice to humans.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Network-based integrated analysis for toxic effects of high-concentration formaldehyde inhalation exposure through the toxicogenomic approach.Scientific reports · 2022Article
- Relationship Between Soluble Urokinase Plasminogen Activator Receptor (suPAR) and Disease Outcome in Adult-Onset Asthma.Journal of asthma and allergy · 2022Article
- Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults.Circulation. Genomic and precision medicine · 2021Article
- Genetic Profile of Endotoxemia Reveals an Association With Thromboembolism and Stroke.Journal of the American Heart Association · 2021Article
- Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation.Frontiers in immunology · 2021Review
- Article
- High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD.International journal of chronic obstructive pulmonary disease · 2020Article
- The biomarkers suPAR and blood eosinophils are associated with hospital readmissions and mortality in asthma - a retrospective cohort study.Respiratory research · 2019Article
- The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target.Brain : a journal of neurology · 2018Article
- Article
- Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma.American journal of respiratory and critical care medicine · 2016Observational
- Adrenal cortex expression quantitative trait loci in a German Holstein × Charolais cross.BMC genetics · 2016Article
- Associations Between Common and Rare Exonic Genetic Variants and Serum Levels of 20 Cardiovascular-Related Proteins: The Tromsø Study.Circulation. Cardiovascular genetics · 2016Article
- Expression of polycomb protein BMI-1 maintains the plasticity of basal bronchial epithelial cells.Physiological reports · 2016Article
- Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma.The European respiratory journal · 2016Article
- The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro.PloS one · 2016Article
- Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD.International journal of chronic obstructive pulmonary disease · 2015Article
- Soluble urokinase-type plasminogen activator receptor as a measure of treatment response in acute exacerbation of COPD.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e TisilogiaArticle
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Authors and funding
14 authors at 9 institutions in 5 countries.
Funding
Abstract
The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17 × 10(-7)), which was also observed in a COPD population (combined P=5.04 × 10(-12)). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects. In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases.
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