ArticleThe Journal of biological chemistry2009
Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers, 3 of them syntheses that pooled it.
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Who cites it
244 citing papers in PubMed, 3 syntheses or guidelines pooled it, 467 citations in OpenAlex.
- Chromosome X-wide association study in case control studies of pathologically confirmed Alzheimer's disease in a European population.Translational psychiatry · 2024Pooled it
- Bibliometric analysis of pyroptosis in pathogenesis and treatment of acute lung injury.Frontiers in medicine · 2024Pooled it
- Role of Inflammasomes in Neuroimmune and Neurodegenerative Diseases: A Systematic Review.Mediators of inflammation · 2018Pooled it
- Targeting biglycan-TLR2/TLR4 interaction with synthetic peptides mitigates inflammation and ameliorates renal function in ischemia-reperfusion injury.Cellular & molecular biology letters · 2026Article
- Extracellular matrix proteoglycans lumican and biglycan promote innate immune signals and viral clearance in HSV-1 infections of mouse corneas.bioRxiv : the preprint server for biology · 2026Article
- Aggrecan and small leucine-rich proteoglycan fragments correlate with Toll-like receptor-2 mediated inflammation in painful degenerative disc disease.The Korean journal of pain · 2026Article
- Extracellular matrix fragments and Toll-like receptor-2: reinforcing the mechanistic bridge from disc degeneration to inflammation in human tissue.The Korean journal of pain · 2026Article
- Interactions between small leucine-rich proteoglycans and proteases: implications for tissue homeostasis and pathology.The FEBS journal · 2026Review
- Biomarker Differences in Aneurysmal Subarachnoid Hemorrhage: A Comparative Study of Patients with and Without Delayed CEREBRAL Ischemia.Neurocritical care · 2026Article
- Structural insights into glycan recognition by plant immune receptors: a comparative perspective with animal innate immune systems.The Plant journal : for cell and molecular biology · 2026Review
- P2X4 receptors on myeloid cells mediate tissue injury in a model of trauma and hemorrhagic shock in male mice.Purinergic signalling · 2026Article
- Molecular mechanisms of acute inflammation: systemic responses and kidney-specific pathophysiology.Function (Oxford, England) · 2026Review
- Enhancer-mediated NR2F2 recruitment activates BGN to promote tumor growth and shape tumor microenvironment in papillary thyroid cancer.Theranostics · 2026Article
- Sulfated Glycosaminoglycans in Inflammation.Advances in experimental medicine and biology · 2026Review
- XBP1s-Orchestrated Soluble Mediators: Participants of Oxidative Stress in Renal Ischemia-Reperfusion Injury Following Donation After Circulatory Death.Mediators of inflammation · 2026Review
- BGN Secreted by Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression via Activation of TLR4-Mediated Erk and NF-κB Signaling Pathways.International journal of molecular sciences · 2025Article
- P2X4 receptors on myeloid cells mediate tissue injury in a murine model of trauma and hemorrhagic shock.Research square · 2025Article
- Nitric oxide modulates UDP-evoked cytosolic transients via P2YScientific reports · 2025Article
- Spinal cord injury and male infertility: Effect of the inflammasome proteins on semen quality.The journal of spinal cord medicine · 2025Article
- What a pain in the back: etiology, diagnosis and future treatment directions for discogenic low back pain.Bone research · 2025Review
184 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The role of endogenous inducers of inflammation is poorly understood. To produce the proinflammatory master cytokine interleukin (IL)-1beta, macrophages need double stimulation with ligands to both Toll-like receptors (TLRs) for IL-1beta gene transcription and nucleotide-binding oligomerization domain-like receptors for activation of the inflammasome. It is particularly intriguing to define how this complex regulation is mediated in the absence of an infectious trigger. Biglycan, a ubiquitous leucine-rich repeat proteoglycan of the extracellular matrix, interacts with TLR2/4 on macrophages. The objective of this study was to define the role of biglycan in the synthesis and activation of IL-1beta. Here we show that in macrophages, soluble biglycan induces the NLRP3/ASC inflammasome, activating caspase-1 and releasing mature IL-1beta without the need for additional costimulatory factors. This is brought about by the interaction of biglycan with TLR2/4 and purinergic P2X(4)/P2X(7) receptors, which induces receptor cooperativity. Furthermore, reactive oxygen species formation is involved in biglycan-mediated activation of the inflammasome. By signaling through TLR2/4, biglycan stimulates the expression of NLRP3 and pro-IL-1beta mRNA. Both in a model of non-infectious inflammatory renal injury (unilateral ureteral obstruction) and in lipopolysaccharide-induced sepsis, biglycan-deficient mice displayed lower levels of active caspase-1 and mature IL-1beta in the kidney, lung, and circulation. Our results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and describe a fundamental paradigm of how tissue stress or injury is monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.