ArticleSurgery2014
Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver.
Article in Surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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Who cites it
82 citing papers in PubMed, 135 citations in OpenAlex.
- Extracellular Vesicle-Mediated Local and Systemic Communication in Metabolic Diseases.International journal of molecular sciences · 2026Review
- Comparative analysis of extracellular vesicles released from resting neutrophils under distinct pharmacological inhibition.Scientific reports · 2026Article
- Extracellular Vesicles in Liver Fibrosis: Pathogenic Messengers, Diagnostic Biomarkers, and Therapeutic Nanovectors.Pharmaceutics · 2026Review
- Extracellular vesicles for targeted drug delivery: advances in surface modification strategies and therapeutic applications.Journal of translational medicine · 2025Review
- Intercellular communication interference through energy metabolism-related exosome secretion inhibition for liver fibrosis treatment.Acta pharmaceutica Sinica. B · 2025Article
- Engineering exosomes for liver disease: a new insight in regenerative medicine and drug delivery.Applied biochemistry and biotechnology · 2025Review
- Emerging insights into mesenchymal stem cells and exosome-based therapies for liver injury.Biomolecules & biomedicine · 2025Review
- Sinusoidal communication in chronic liver disease.Clinical and molecular hepatology · 2025Review
- Extracellular Vesicles in Viral Liver Diseases.Viruses · 2024Review
- Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes.International journal of molecular sciences · 2024Article
- Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis.Science advances · 2024Article
- Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis.Clinical nutrition ESPEN · 2024Article
- Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases.Biomolecules · 2024Review
- Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases.Journal of clinical and translational hepatology · 2023Review
- Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin.International journal of molecular sciences · 2023Article
- CCN Proteins (Cellular Communication Network Factors): Expanding Their Repertoire Toward a New Concept.Methods in molecular biology (Clifton, N.J.) · 2023Article
- [Effect of macrophage-derived exosomes on promoting hepatic stellate cell activation and platelet-derived growth factor expression].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- Exosomal microRNAs and Progression of Nonalcoholic Steatohepatitis (NASH).International journal of molecular sciences · 2022Review
- The Role of Extracellular Vesicles in Liver Pathogenesis.The American journal of pathology · 2022Review
- Pathological Contribution of Extracellular Vesicles and Their MicroRNAs to Progression of Chronic Liver Disease.Biology · 2022Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundFibrogenic pathways in the liver are principally regulated by hepatic stellate cells (HSC), which produce and respond to fibrotic mediators such as connective tissue growth factor (CCN2). The aim of this study was to determine whether CCN2 is shuttled between HSC in membranous nanovesicles, or "exosomes."
methodsExosomes were incubated with HSC after isolation from conditioned medium of control or CCN2-green fluorescent protein (GFP)-transfected primary mouse HSC or human LX-2 HSC. Some exosomes were stained fluorescently with PKH26. HSC co-culture experiments were performed in the presence of GW4869 exosome inhibitor. CCN2 or CCN2-GFP were evaluated by quantitative real-time polymerase chain reaction or Western blot.
resultsHSC-derived exosomes contained CCN2 or CCN2 mRNA, each of which increased in concentration during HSC activation or after transfection of HSC with CCN2-GFP. Exosomes, stained with either PKH26 or purified from CCN2-GFP-transfected cells, were taken up by activated or quiescent HSC resulting in CCN2-GFP delivery, as shown by their direct addition to recipient cells or by the GW4869-dependency of donor HSC.
conclusionCCN2 is packaged into secreted, nano-sized exosomes that mediate its intercellular transfer between HSC. Exosomal CCN2 may amplify or fine tune fibrogenic signaling and, in conjunction with other exosome constituents, may have utility as a noninvasive biomarker to assess hepatic fibrosis.
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