ArticleMolecular & cellular proteomics : MCP2013
Monosodium urate activates Src/Pyk2/PI3 kinase and cathepsin dependent unconventional protein secretion from human primary macrophages.
Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Targeting SAA expression via siRNA mitigates preterm birth induced by maternal inflammation.Frontiers in pharmacology · 2026Article
- Hyperuricemia-induced complications: dysfunctional macrophages serve as a potential bridge.Frontiers in immunology · 2025Review
- Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute β-amyloid infusion model.Journal of neuroinflammation · 2024Article
- Extracellular Vesicles inInternational journal of molecular sciences · 2024Review
- Alterations of Hepatic Lipidome Occur in a Gouty Model: A Shotgun Lipidomics Study.Journal of inflammation research · 2024Article
- Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells.Cell death & disease · 2023Article
- Protease-Activated Receptor-2 and Phospholipid Metabolism Analysis in Hyperuricemia-Induced Renal Injury.Mediators of inflammation · 2023Article
- Lipidomics analysis facilitate insight into the molecular mechanisms of urate nephropathy in a gout model induced by combination of MSU crystals injection and high-fat diet feeding.Frontiers in molecular biosciences · 2023Article
- Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease.Renal failure · 2022Review
- Mouse Modeling Dissecting Macrophage-Breast Cancer Communication Uncovered Roles of PYK2 in Macrophage Recruitment and Breast Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Inflammasome-induced extracellular vesicles harbour distinct RNA signatures and alter bystander macrophage responses.Journal of extracellular vesicles · 2021Article
- Hyperuricemia causes kidney damage by promoting autophagy and NLRP3-mediated inflammation in rats with urate oxidase deficiency.Disease models & mechanisms · 2021Article
- Proteasome α6 Subunit Negatively Regulates the JAK/STAT Pathway and Blood Cell Activation inFrontiers in immunology · 2021Article
- Rab GTPase Mediating Regulation of NALP3 in Colorectal Cancer.Molecules (Basel, Switzerland) · 2020Article
- Tumor-derived exosomes (TDEs): How to avoid the sting in the tail.Medicinal research reviews · 2020Review
- Research Advances in the Mechanisms of Hyperuricemia-Induced Renal Injury.BioMed research international · 2020Review
- Modulating Cytokine Production via Select Packaging and Secretion From Extracellular Vesicles.Frontiers in immunology · 2020Review
- Extracellular vesicles as cancer liquid biopsies: from discovery, validation, to clinical application.Lab on a chip · 2019Review
- Suppression of Syk activation by resveratrol inhibits MSU crystal-induced inflammation in human monocytes.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monosodium urate (MSU) is an endogenous danger signal that is crystallized from uric acid released from injured cells. MSU is known to activate inflammatory response in macrophages but the molecular mechanisms involved have remained uncharacterized. Activated macrophages start to secrete proteins to activate immune response and to recruit other immune cells to the site of infection and/or tissue damage. Secretome characterization after activation of innate immune system is essential to unravel the details of early phases of defense responses. Here, we have analyzed the secretome of human primary macrophages stimulated with MSU using quantitative two-dimensional gel electrophoresis based proteomics as well as high-throughput qualitative GeLC-MS/MS approach combining protein separation by SDS-PAGE and protein identification by liquid chromatography-MS/MS. Both methods showed that MSU stimulation induced robust protein secretion from lipopolysaccharide-primed human macrophages. Bioinformatic analysis of the secretome data showed that MSU stimulation strongly activates unconventional, vesicle mediated protein secretion. The unconventionally secreted proteins included pro-inflammatory cytokines like IL-1β and IL-18, interferon-induced proteins, and danger signal proteins. Also active forms of lysosomal proteases cathepsins were secreted on MSU stimulation, and cathepsin activity was essential for MSU-induced unconventional protein secretion. Additionally, proteins associated to phosphorylation events including Src family tyrosine kinases were increased in the secretome of MSU-stimulated cells. Our functional studies demonstrated that Src, Pyk2, and PI3 kinases act upstream of cathepsins to activate the overall protein secretion from macrophages. In conclusion, we provide the first comprehensive characterization of protein secretion pathways activated by MSU in human macrophages, and reveal a novel role for cathepsins and Src, Pyk2, PI3 kinases in the activation of unconventional protein secretion.
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