ArticleThe Journal of biological chemistry2018
Hyaluronan content governs tissue stiffness in pancreatic islet inflammation.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- 4-Methylumbelliferone for type 1 diabetes therapy: evidence for β-cell protection via EGFR/PI3K/Akt signaling.Journal of endocrinological investigation · 2026Article
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Hyaluronan induces ERK activation with minimal transcriptomic changes in pancreatic α-cells.Biochemistry and biophysics reports · 2026Article
- The predictive value of hyaluronic acid for the severity and prognosis of COVID-19: a retrospective multicenter cohort study.Annals of medicine · 2025Article
- Dual Effect of 4-Methylumbelliferone on INS1E Cells: Enhancing Migration and Glucose-Stimulated Insulin Secretion.International journal of molecular sciences · 2025Article
- Hyaluronan Accumulates in Inflamed Lymph Nodes and Promotes B-Cell Activation.Proteoglycan research · 2025Article
- Mechanosensitivity of macrophage polarization: comparing small molecule leukadherin-1 to substrate stiffness.Frontiers in immunology · 2025Article
- Beneficial Actions of 4-Methylumbelliferone in Type 1 Diabetes by Promoting β Cell Renewal and Inhibiting Dedifferentiation.Biomedicines · 2024Article
- Mechanical Properties of Inflamed Appendix Tissues.Biomedicines · 2024Article
- Article
- Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma.Scientific reports · 2024Article
- Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated CaMatrix biology plus · 2024Article
- Autoimmune diseases: targets, biology, and drug discovery.Acta pharmacologica Sinica · 2024Review
- Cortical matrix remodeling as a hallmark of relapsing-remitting neuroinflammation in MR elastography and quantitative MRI.Acta neuropathologica · 2024Article
- Multiple aspects of matrix stiffness in cancer progression.Frontiers in oncology · 2024Review
- Hydration State and Hyaluronidase Treatment Significantly Affect Porcine Vocal Fold Biomechanics.Journal of voice : official journal of the Voice Foundation · 2023Article
- Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Selective isolation of hyaluronan by solid phase adsorption to silica.Analytical biochemistry · 2022Article
- Methods for isolating and analyzing physiological hyaluronan: a review.American journal of physiology. Cell physiology · 2022Review
- Integrin Regulated Autoimmune Disorders: Understanding the Role of Mechanical Force in Autoimmunity.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel "bed of nails"-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared with controls. Conversely, treatment with 4-methylumbelliferone, a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content, we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses.
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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.