ArticleThe Journal of biological chemistry2013
The hyaluronan receptor for endocytosis (HARE) activates NF-κB-mediated gene expression in response to 40-400-kDa, but not smaller or larger, hyaluronans.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
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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
45 citing papers in PubMed, 78 citations in OpenAlex.
- Low molecular weight hyaluronan activates cytosolic phospholipase A2α and eicosanoid production in monocytes and macrophages.The Journal of biological chemistry · 2014Trial
- Microbial Hyaluronidases: From Obscure Virulence Factors to Promising Therapeutic Targets.Biomolecules · 2026Review
- Review
- Macrophage targeting precision nanomedicine utilizing ROS-responsive metallozyme-loaded nanomicelle for enhanced treatment of gout-induced inflammation.Science and technology of advanced materials · 2025Article
- Review
- Hyaluronan and Reactive Oxygen Species Signaling-Novel Cues from the Matrix?Antioxidants (Basel, Switzerland) · 2023Review
- Enhanced Tumor Accumulation of Low-Molecular-Weight Hyaluronic Acid/Chitosan Nanocomplexes for Photothermal Therapy.Pharmaceutics · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Hyaluronan breakdown by snake venom hyaluronidases: From toxins delivery to immunopathology.Frontiers in immunology · 2023Review
- The New General Biological Property of Stem-like Tumor Cells (Part II: Surface Molecules, Which Belongs to Distinctive Groups with Particular Functions, Form a Unique Pattern Characteristic of a Certain Type of Tumor Stem-like Cells).International journal of molecular sciences · 2022Article
- Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity.Biomolecules · 2022Review
- Hyaluronic Acid: Known for Almost a Century, but Still in Vogue.Pharmaceutics · 2022Review
- Reduction ofFrontiers in cardiovascular medicine · 2022Article
- Immunomodulatory Nanomedicine for the Treatment of Atherosclerosis.Journal of clinical medicine · 2021Review
- Nanoparticle-Based Approaches towards the Treatment of Atherosclerosis.Pharmaceutics · 2020Review
- Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling.Cells · 2020Review
- Role of the Hyaluronan Receptor, Stabilin-2/HARE, in Health and Disease.International journal of molecular sciences · 2020Review
- Development and application of hyaluronic acid in tumor targeting drug delivery.Acta pharmaceutica Sinica. B · 2019Review
- Ligand Binding and Signaling of HARE/Stabilin-2.Biomolecules · 2019Review
- Hyaluronan biology: A complex balancing act of structure, function, location and context.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The hyaluronan (HA) receptor for endocytosis (HARE; Stabilin-2) binds and clears 14 different ligands, including HA and heparin, via clathrin-mediated endocytosis. HA binding to HARE stimulates ERK1/2 activation (Kyosseva, S. V., Harris, E. N., and Weigel, P. H. (2008) J. Biol. Chem. 283, 15047-15055). To assess a possible HA size dependence for signaling, we tested purified HA fractions of different weight-average molar mass and with narrow size distributions and Select-HA(TM) for stimulation of HARE-mediated gene expression using an NF-κB promoter-driven luciferase reporter system. Human HARE-mediated gene expression was stimulated in a dose-dependent manner with small HA (sHA) >40 kDa and intermediate HA (iHA) <400 kDa. The hyperbolic dose response saturated at 20-50 nM with an apparent K(m) ~10 nM, identical to the Kd for HA-HARE binding. Activation was not detected with oligomeric HA (oHA), sHA <40 kDa, iHA >400 kDa, or large HA (lHA). Similar responses occurred with rat HARE. Activation by sHA-iHA was blocked by excess nonsignaling sHA, iHA, or lHA, deletion of the HA-binding LINK domain, or HA-blocking antibody. Endogenous NF-κB activation also occurred in the absence of luciferase plasmids, as assessed by degradation of IκB-α. ERK1/2 activation was also HA size-dependent. The results show that HA-HARE interactions stimulate NF-κB-activated gene expression and that HARE senses a narrow size range of HA degradation products. We propose a model in which optimal length HA binds multiple HARE proteins to allow cytoplasmic domain interactions that stimulate intracellular signaling. This HARE signaling system during continuous HA clearance could monitor the homeostasis of tissue biomatrix turnover throughout the body.
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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.