ArticleThe Journal of biological chemistry2015
Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
What it found
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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
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis.Clinics (Sao Paulo, Brazil)Pooled it
- Adipose-Derived Mesenchymal Stem Cell Exosome miR-146a-5p Attenuates TGF-β2-Induced Transformation of Human Tenon's Capsule Fibroblasts by Targeting SMAD4.Investigative ophthalmology & visual science · 2026Article
- Bioengineered Exosome-Loaded Immunomodulatory Bioadhesive Spray Reverses Liver Fibrosis and Metabolic Dysfunction That Triggers Beneficial Gut-Liver Crosstalk in Chronic Fatty Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Extracellular Vesicles in Liver Fibrosis: Pathogenic Messengers, Diagnostic Biomarkers, and Therapeutic Nanovectors.Pharmaceutics · 2026Review
- Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.Reproductive biology and endocrinology : RB&E · 2025Review
- Cutting-edge insights into liver fibrosis: advanced therapeutic strategies and future perspectives using engineered mesenchymal stem cell-derived exosomes.Drug delivery and translational research · 2025Review
- The role of hepatic sinusoidal microenvironment in NASH: pathogenesis, animal models, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis.Frontiers in immunology · 2025Article
- Sinusoidal communication in chronic liver disease.Clinical and molecular hepatology · 2025Review
- Dynamic role of exosomal long non-coding RNA in liver diseases: pathogenesis and diagnostic aspects.Hepatology international · 2024Review
- Extracellular Vesicles in Viral Liver Diseases.Viruses · 2024Review
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Angiocrine signaling in sinusoidal homeostasis and liver diseases.Journal of hepatology · 2024Review
- Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma.Cancers · 2024Review
- Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis.Science advances · 2024Article
- The potential role of extracellular vesicles as hepatic diagnostic and therapeutic tools: Can the dream come true?iLIVER · 2024Review
- Role of Hepatic Stellate and Liver Sinusoidal Endothelial Cells in a Human Primary Cell Three-Dimensional Model of Nonalcoholic Steatohepatitis.The American journal of pathology · 2024Article
- Liver sinusoidal endothelial cells as potential drivers of liver fibrosis (Review).Molecular medicine reports · 2024Article
- Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases.Biomolecules · 2024Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Exosomes are cell-derived extracellular vesicles thought to promote intercellular communication by delivering specific content to target cells. The aim of this study was to determine whether endothelial cell (EC)-derived exosomes could regulate the phenotype of hepatic stellate cells (HSCs). Initial microarray studies showed that fibroblast growth factor 2 induced a 2.4-fold increase in mRNA levels of sphingosine kinase 1 (SK1). Exosomes derived from an SK1-overexpressing EC line increased HSC migration 3.2-fold. Migration was not conferred by the dominant negative SK1 exosome. Incubation of HSCs with exosomes was also associated with an 8.3-fold increase in phosphorylation of AKT and 2.5-fold increase in migration. Exosomes were found to express the matrix protein and integrin ligand fibronectin (FN) by Western blot analysis and transmission electron microscopy. Blockade of the FN-integrin interaction with a CD29 neutralizing antibody or the RGD peptide attenuated exosome-induced HSC AKT phosphorylation and migration. Inhibition of endocytosis with transfection of dynamin siRNA, the dominant negative dynamin GTPase construct Dyn2K44A, or the pharmacological inhibitor Dynasore significantly attenuated exosome-induced AKT phosphorylation. SK1 levels were increased in serum exosomes derived from mice with experimental liver fibrosis, and SK1 mRNA levels were up-regulated 2.5-fold in human liver cirrhosis patient samples. Finally, S1PR2 inhibition protected mice from CCl4-induced liver fibrosis. Therefore, EC-derived SK1-containing exosomes regulate HSC signaling and migration through FN-integrin-dependent exosome adherence and dynamin-dependent exosome internalization. These findings advance our understanding of EC/HSC cross-talk and identify exosomes as a potential target to attenuate pathobiology signals.
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What OpenQuestion holds
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.