Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration
| Autor: | Erik Schadde, Roland H. Wenger, Donat R. Spahn, Christa Booy, Vartan Kurtcuoglu, Rita Fatzer, Martin Schläpfer, Costica Aloman, Birke Bartosch, Romain Parent, Beatrice Beck Schimmer, Diane de Zélicourt, Konstantin Dirscherl, Birgit Roth Z'graggen, Renata Flury-Frei |
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| Přispěvatelé: | Universität Zürich [Zürich] = University of Zurich (UZH), Cantonal Hospital Winterthur [Zurich, Suisse], Rush University Medical Center [Chicago], Pathogenesis of viral hepatitis [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Illinois [Chicago] (UIC), University of Illinois System, This work was supported by Swiss National Science Foundation, Bern, Switzerland, Grant Nr. 310030_179247 (BBS) and a grant from the Jubilaeumsstiftung der Schweizerischen Mobiliar Genossenschaft, Bern, Switzerland (ES)., University of Zürich [Zürich] (UZH), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Schadde, Erik, Bodescot, Myriam |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Angiogenesis 10216 Institute of Anesthesiology lcsh:Medicine 610 Medicine & health [SDV.BC]Life Sciences [q-bio]/Cellular Biology Models Biological Article 10052 Institute of Physiology Transcriptome 03 medical and health sciences 0302 clinical medicine Hepatic stellate cells In vivo medicine Animals Hypoxia lcsh:Science [SDV.BC] Life Sciences [q-bio]/Cellular Biology Cell Proliferation 1000 Multidisciplinary Multidisciplinary Neovascularization Pathologic Chemistry lcsh:R [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Hypoxia (medical) biochemical phenomena metabolism and nutrition bacterial infections and mycoses [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Liver regeneration In vitro Liver Regeneration Rats Crosstalk (biology) Mechanisms of disease 030104 developmental biology 030220 oncology & carcinogenesis Models Animal Hepatic stellate cell Cancer research lcsh:Q Disease Susceptibility medicine.symptom Biomarkers |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.4392. ⟨10.1038/s41598-020-60709-9⟩ Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports, 2020, 10 (1), pp.4392. ⟨10.1038/s41598-020-60709-9⟩ |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-60709-9⟩ |
| Popis: | Portal vein ligation (PVL) induces liver growth prior to resection. Associating liver partition and portal vein ligation (PVL plus transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to PVL both accelerate growth via stabilization of HIF-α subunits. This study aims at clarifying the crosstalk of hepatocytes (HC), hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) in accelerated liver growth. In vivo, liver volume, HC proliferation, vascular density and HSC activation were assessed in PVL, ALPPS, PVL+DMOG and DMOG alone. Proliferation of HC, HSC and LSEC was determined under DMOG in vitro. Conditioned media experiments of DMOG-exposed cells were performed. ALPPS and PVL+DMOG accelerated liver growth and HC proliferation in comparison to PVL. DMOG alone did not induce HC proliferation, but led to increased vascular density, which was also observed in ALPPS and PVL+DMOG. Activated HSC were detected in ALPPS, PVL+DMOG and DMOG, again not in PVL. In vitro, DMOG had no proliferative effect on HC, but conditioned supernatant of DMOG-treated HSC induced VEGF-dependent proliferation of LSEC. Transcriptome analysis confirmed activation of proangiogenic factors in hypoxic HSC. Hypoxia signaling in HSC induces VEGF-dependent angiogenesis. HSC play a crucial role in the cellular crosstalk of rapid liver regeneration. |
| Databáze: | OpenAIRE |
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