ArticleMatrix biology : journal of the International Society for Matrix Biology2016
Bimodal role of NADPH oxidases in the regulation of biglycan-triggered IL-1β synthesis.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Targeting biglycan-TLR2/TLR4 interaction with synthetic peptides mitigates inflammation and ameliorates renal function in ischemia-reperfusion injury.Cellular & molecular biology letters · 2026Article
- The core mechanism of hypertension-linked renal fibrosis: "RAAS-ROS-inflammation-fibrosis" axis.iScience · 2026Review
- Innovative mitochondria-based holistic 3PM approach to female health status: Facts and outlook.The EPMA journal · 2026Article
- Enhancer-mediated NR2F2 recruitment activates BGN to promote tumor growth and shape tumor microenvironment in papillary thyroid cancer.Theranostics · 2026Article
- Polydatin alleviates mitochondrial damage and apoptosis of lung epithelial cells by inhibiting toll-like receptor 4-dependent macrophage activation in asthma.Animal models and experimental medicine · 2026Article
- XBP1s-Orchestrated Soluble Mediators: Participants of Oxidative Stress in Renal Ischemia-Reperfusion Injury Following Donation After Circulatory Death.Mediators of inflammation · 2026Review
- PLGA-Based Micro/Nanoparticles: An Overview of Their Applications in Respiratory Diseases.International journal of molecular sciences · 2023Review
- Matrix proteoglycans in tumor inflammation and immunity.American journal of physiology. Cell physiology · 2022Review
- Proteoglycans in Toll-like receptor responses and innate immunity.American journal of physiology. Cell physiology · 2022Review
- Macrophage-extracellular matrix interactions: Perspectives for tissue engineered heart valve remodeling.Frontiers in cardiovascular medicine · 2022Review
- Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction by Inhibiting TLR4-NOX1/ROS Signaling Pathway in Caco-2 Cells.Frontiers in pharmacology · 2022Article
- Roles of Two Small Leucine-Rich Proteoglycans Decorin and Biglycan in Pregnancy and Pregnancy-Associated Diseases.International journal of molecular sciences · 2021Review
- The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis.Brain : a journal of neurology · 2021Review
- Article
- The Role of Decorin and Biglycan Signaling in Tumorigenesis.Frontiers in oncology · 2021Review
- Communications via the Small Leucine-rich Proteoglycans: Molecular Specificity in Inflammation and Autoimmune Diseases.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Integral Roles of Specific Proteoglycans in Hair Growth and Hair Loss: Mechanisms behind the Bioactivity of Proteoglycan Replacement Therapy with Nourkrin® with Marilex® in Pattern Hair Loss and Telogen Effluvium.Dermatology research and practice · 2020Review
- Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-Mediators of inflammation · 2020Article
- Expression and localization of the small proteoglycans decorin and biglycan in articular cartilage of Kashin-Beck disease and rats induced by T-2 toxin and selenium deficiency.Glycoconjugate journal · 2019Article
- Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction by Suppressing Toll-Like Receptor 4 (TLR4)/NADPH Oxidase 2 (NOX2) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Biglycan, a ubiquitous proteoglycan, acts as a danger signal when released from the extracellular matrix. As such, biglycan triggers the synthesis and maturation of interleukin-1β (IL-1β) in a Toll-like receptor (TLR) 2-, TLR4-, and reactive oxygen species (ROS)-dependent manner. Here, we discovered that biglycan autonomously regulates the balance in IL-1β production in vitro and in vivo by modulating expression, activity and stability of NADPH oxidase (NOX) 1, 2 and 4 enzymes via different TLR pathways. In primary murine macrophages, biglycan triggered NOX1/4-mediated ROS generation, thereby enhancing IL-1β expression. Surprisingly, biglycan inhibited IL-1β due to enhancement of NOX2 synthesis and activation, by selectively interacting with TLR4. Synthesis of NOX2 was mediated by adaptor molecule Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF). Via myeloid differentiation primary response protein (MyD88) as well as Rac1 activation and Erk phosphorylation, biglycan triggered translocation of the cytosolic NOX2 subunit p47(phox) to the plasma membrane, an obligatory step for NOX2 activation. In contrast, by engaging TLR2, soluble biglycan stimulated the expression of heat shock protein (HSP) 70, which bound to NOX2, and consequently impaired the inhibitory function of NOX2 on IL-1β expression. Notably, a genetic background lacking biglycan reduced HSP70 expression, rescued the enhanced renal IL-1β production and improved kidney function of Nox2(-/y) mice in a model of renal ischemia reperfusion injury. Here, we provide a novel mechanism where the danger molecule biglycan influences NOX2 synthesis and activation via different TLR pathways, thereby regulating inflammation severity. Thus, selective inhibition of biglycan-TLR2 or biglycan-TLR4 signaling could be a novel therapeutic approach in ROS-mediated inflammatory diseases.
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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.