ArticleScience translational medicine2019
Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.Clinical and translational medicine · 2024Pooled it
- 3D Liver Fibrosis Models in Lab: A Novel Modality for Drug Screening.Pharmacology research & perspectives · 2026Review
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- Versican regulating viscoelasticity drives pleural fibrosis via mechanotransductive signaling.JCI insight · 2026Article
- Article
- Metabolomic Profiling of Vitreous Humor Reveals Distinct Metabolic Signatures in Proliferative Vitreoretinopathy.Investigative ophthalmology & visual science · 2026Article
- Orcinol glucoside ameliorates pulmonary fibrosis by suppressing hyaluronic acid synthesis and macrophage M2 polarization via targeting hyaluronic acid synthase 2.International journal of molecular medicine · 2026Article
- Pirfenidone attenuates urethral stricture after injury by inhibiting Gli2 mediated HAS2 expression in fibroblasts.Journal of molecular histology · 2026Article
- Lymphatic disruption drives lung transplant fibrosis through interleukin-1-mediated hyaluronan accumulation.Science translational medicine · 2026Article
- Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling.Nature communications · 2026Article
- The myofascial rheostat: hyaluronan molecular weight dynamics and purinergic signalling as a physiological feedback system.Frontiers in physiology · 2026Review
- Therapeutic targeting of the AMPK-Has1 complex formation ameliorates metabolic dysfunction-associated steatohepatitis in mice.Theranostics · 2026Article
- Article
- From Bench to Bedside: Multifunctional Nanoplatforms in the Fight Against Non-alcoholic Fatty Liver Disease.International journal of nanomedicine · 2026Review
- Understanding Fascial Tissue on the Molecular Level-How Its Unique Properties Enable Adaptation or Dysfunction.International journal of molecular sciences · 2025Review
- Next-Generation Hydrogels for Biliary Organoid Engineering.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Hyaluronic Acid in Liver Fibrosis: Role in Inflammation, Tissue Remodeling, and Disease Progression.International journal of molecular sciences · 2025Review
- Intestinal Ischemia/Reperfusion Injury Influences Hyaluronan Homeostasis in the Rat Brain.International journal of molecular sciences · 2025Article
- Intercellular communication interference through energy metabolism-related exosome secretion inhibition for liver fibrosis treatment.Acta pharmaceutica Sinica. B · 2025Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
Abstract
Hyaluronan (HA), a major extracellular matrix glycosaminoglycan, is a biomarker for cirrhosis. However, little is known about the regulatory and downstream mechanisms of HA overproduction in liver fibrosis. Hepatic HA and HA synthase 2 (HAS2) expression was elevated in both human and murine liver fibrosis. HA production and liver fibrosis were reduced in mice lacking HAS2 in hepatic stellate cells (HSCs), whereas mice overexpressing HAS2 had exacerbated liver fibrosis. HAS2 was transcriptionally up-regulated by transforming growth factor-β through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4 (TLR4), and newly identified downstream effector Notch1. Inhibition of HA synthesis by 4-methylumbelliferone reduced HSC activation and liver fibrosis in mice. Our study provides evidence that HAS2 actively synthesizes HA in HSCs and that it promotes HSC activation and liver fibrosis through Notch1. Targeted HA inhibition may have potential to be an effective therapy for liver fibrosis.
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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.