ArticleISRN nephrology2014
Hyaluronan is not a ligand but a regulator of toll-like receptor signaling in mesangial cells: role of extracellular matrix in innate immunity.
Article in ISRN nephrology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
32 citing papers in PubMed.
- Naive CD4iScience · 2026Article
- Nitric oxide-releasing hyaluronic acid as an antibacterial and immunomodulatory acne therapeutic.RSC advances · 2026Article
- The Challenges of Local Intra-Articular Therapy.Medicina (Kaunas, Lithuania) · 2024Review
- Hyaluronic Acid Hampers the Inflammatory Response Elicited by Extracellular Vesicles from Activated Monocytes in Human Chondrocytes.Pharmaceutics · 2024Article
- Biomimetic Hyaluronan Binding Biomaterials to Capture the Complex Regulation of Hyaluronan in Tissue Development and Function.Biomimetics (Basel, Switzerland) · 2024Review
- Modern Approaches in Wounds Management.Polymers · 2023Review
- Mast cell tolerance in the skin microenvironment to commensal bacteria is controlled by fibroblasts.Cell reports · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Activation of sperm Toll-like receptor 2 induces hyperactivation to enhance the penetration to mucus and uterine glands: a trigger for the uterine inflammatory cascade in cattle.Frontiers in immunology · 2023Article
- Hyaluronan regulates sperm-induced inflammatory response by enhancing sperm attachment to bovine endometrial epithelial cellsFrontiers in endocrinology · 2023Article
- Hyaluronic Acid: Known for Almost a Century, but Still in Vogue.Pharmaceutics · 2022Review
- Autocrine Hyaluronan Influences Sprouting and Lumen Formation During HUVEC Tubulogenesis In Vitro.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Article
- Progress in drug delivery system for fibrosis therapy.Asian journal of pharmaceutical sciences · 2021Review
- TLR4 Signaling by Heme and the Role of Heme-Binding Blood Proteins.Frontiers in immunology · 2020Review
- Article
- Hyaluronic Acid: Incorporating the Bio into the Material.ACS biomaterials science & engineering · 2019Article
- Dissecting the role of hyaluronan synthases in the tumor microenvironment.The FEBS journal · 2019Review
- Hyaluronan in inflammatory bowel disease: Cross-linking inflammation and coagulation.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Degradation of tumour stromal hyaluronan by small extracellular vesicle-PH20 stimulates CD103Journal of extracellular vesicles · 2019Article
- Regulation of Immune Responses and Chronic Inflammation by Fibroblast-Like Synoviocytes.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glomerular mesangial cells (MC), like most cell types secrete hyaluronan (HA), which attached to the cell surface via CD44, is the backbone of a hydrophilic gel matrix around these cells. Reduced extracellular matrix thickness and viscosity result from HA cleavage during inflammation. HA fragments were reported to trigger innate immunity via Toll-like receptor-(TLR-) 2 and/or TLR4 in immune cells. We questioned whether HA fragments also regulate the immunostimulatory capacity of smooth muscle cell-like MC. LPS (TLR4-ligand) and PAM3CysSK4 (TLR2-ligand) induced IL-6 secretion in MC; highly purified endotoxin-free HA < 3000 Da up to 50 μ g/mL did not. Bovine-testis-hyaluronidase from was used to digest MC-HA into HA fragments of different size directly in the cell culture. Resultant HA fragments did not activate TLR4-deficient MC, while TLR2-deficient MC responded to LPS-contamination of hyaluronidase, not to produced HA fragments. Hyaluronidase increased the stimulatory effect of TLR2-/-3/-5 ligands on their TLR-receptors in TLR4-deficient MC, excluding any effect by LPS-contamination. Supplemented heparin suppressed every stimulatory effect in a dose-dependent manner. We conclude that the glycosaminoglycan HA creates a pericellular jelly barrier, which covers surface receptors like the TLRs. Barrier-thickness and viscosity balanced by HA-synthesis and degradation and the amount of HA-receptors on the cell surface regulate innate immunity via the accessibility of the receptors.
Identifiers
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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.