- Exosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury. In the current study, we sought to determine if the regulatory effects of CXCR1 and CXCR2 on liver recovery and regeneration might occur via altered release of hepatocyte exosomes. We found that hepatocyte release of exosomes was dependent upon CXCR1 and CXCR2. CXCR1-deficient hepatocytes produced fewer exosomes, whereas CXCR2-deficient hepatocytes produced more exosomes compared to their wild-type controls. In CXCR2-deficient hepatocytes, there was increased activity of neutral sphingomyelinase (Nsm) andExosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury. In the current study, we sought to determine if the regulatory effects of CXCR1 and CXCR2 on liver recovery and regeneration might occur via altered release of hepatocyte exosomes. We found that hepatocyte release of exosomes was dependent upon CXCR1 and CXCR2. CXCR1-deficient hepatocytes produced fewer exosomes, whereas CXCR2-deficient hepatocytes produced more exosomes compared to their wild-type controls. In CXCR2-deficient hepatocytes, there was increased activity of neutral sphingomyelinase (Nsm) and intracellular ceramide. CXCR1-deficient hepatocytes had no alterations in Nsm activity or ceramide production. Interestingly, exosomes from CXCR1-deficient hepatocytes had no effect on hepatocyte proliferation, due to a lack of neutral ceramidase and sphingosine kinase. The data demonstrate that CXCR1 and CXCR2 regulate hepatocyte exosome release. The mechanism utilized by CXCR1 remains elusive, but CXCR2 appears to modulate Nsm activity and resultant production of ceramide to control exosome release. CXCR1 is required for packaging of enzymes into exosomes that mediate their hepatocyte proliferative effect.…
MetadatenVerfasserangaben: | Hiroyuki Nojima, Takanori Konishi, Christopher M. Freeman, Rebecca M. Schuster, Lukasz JaptokGND, Burkhard KleuserORCiDGND, Michael J. Edwards, Erich GulbinsORCiDGND, Alex B. Lentsch |
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URN: | urn:nbn:de:kobv:517-opus4-410885 |
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DOI: | https://doi.org/10.25932/publishup-41088 |
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ISSN: | 1866-8372 |
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Titel des übergeordneten Werks (Englisch): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
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Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (538) |
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Publikationstyp: | Postprint |
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Sprache: | Englisch |
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Datum der Erstveröffentlichung: | 21.01.2019 |
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Erscheinungsjahr: | 2016 |
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Veröffentlichende Institution: | Universität Potsdam |
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Datum der Freischaltung: | 21.01.2019 |
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Freies Schlagwort / Tag: | ceramide; hepatic ischemia-reperfusion; homolog; injury; ischemia/reperfusion; liver-regeneration; mechanisms; mice; neutrophil; recovery |
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Ausgabe: | 538 |
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Seitenanzahl: | 15 |
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Quelle: | PLOS ONE 11 (2016) 8, Art. e0161443 DOI 10.1371/journal.pone.0161443 |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 50 Naturwissenschaften / 500 Naturwissenschaften und Mathematik |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access |
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Fördermittelquelle: | Public Library of Science (PLOS) |
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Lizenz (Deutsch): | CC-BY - Namensnennung 4.0 International |
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