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| Verfasst von: | Breitkopf-Heinlein, Katja [VerfasserIn]  |
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| | Sawitza, Iris [VerfasserIn] |
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| | Westhoff, Jens [VerfasserIn] |
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| | Wickert, Lucia [VerfasserIn] |
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| | Dooley, Steven [VerfasserIn] |
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| | Gressner, Axel M. [VerfasserIn] |
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| Titel: | Thrombospondin 1 acts as a strong promoter of transforming growth factor β effects via two distinct mechanisms in hepatic stellate cells |
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| Verf.angabe: | K. Breitkopf, I. Sawitza, J.H. Westhoff, L. Wickert, S. Dooley, A.M. Gressner |
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| E-Jahr: | 2005 |
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| Jahr: | April 14, 2005 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 23.06.2022 |
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| Titel Quelle: | Enthalten in: Gut |
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| Ort Quelle: | London : BMJ Publishing Group, 1960 |
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| Jahr Quelle: | 2005 |
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| Band/Heft Quelle: | 54(2005), 5, Seite 673-681 |
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| ISSN Quelle: | 1468-3288 |
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| Abstract: | Background and aims: Thrombospondin 1 (TSP-1) is an important activator of latent transforming growth factor β (TGF-β) but little is known of the expression patterns and functions of TSP-1 in liver cells. We therefore analysed if and how TSP-1 acts on TGF-β during fibrogenesis. - Methods and results: Using reverse transcription-polymerase chain reaction, we demonstrated that hepatocytes from normal liver expressed no TSP-1 mRNA whereas Kupffer cells and sinusoidal endothelial cells did. TSP-1 mRNA and protein were detected in quiescent and activated cultured hepatic stellate cells (HSC) and TSP-1 expression was highly inducible by platelet derived growth factor BB (PDGF-BB) and, to a lesser extent, by tumour necrosis factor α in activated HSC. Furthermore, addition of PDGF-BB directly led to enhanced TGF-β mRNA expression and a TSP-1 dependent increase in TGF-β/Smad signalling. Using either a peptide specifically blocking the interaction of TSP-1 with latent TGF-β or antibodies against TSP-1 not only abrogated activation of latent TGF-β but also reduced the effects of the active dimer itself. - Conclusions: Our data suggest that TSP-1 expression is important for TGF-β effects and that it is regulated by the profibrogenic mediator PDGF-BB in HSC. Furthermore, the presence of TSP-1 seems to be a prerequisite for effective signal transduction by active TGF-β not only in rat HSC but also in other cell types such as human dermal fibroblasts. |
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| DOI: | doi:10.1136/gut.2004.042911 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1136/gut.2004.042911 |
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| | Volltext: https://gut.bmj.com/content/54/5/673 |
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| | DOI: https://doi.org/10.1136/gut.2004.042911 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | BDL, bile duct ligation |
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| | FCS, fetal calf serum |
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| | fibrosis |
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| | HSC, hepatic stellate cells |
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| | IL-6, interleukin 6 |
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| | LAP, latency associated peptide |
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| | liver |
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| | LTBP, latent TGF-β binding protein |
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| | MFB, myofibroblasts |
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| | PDGF-BB, platelet derived growth factor BB |
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| | platelet derived growth factor |
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| | RT-PCR, reverse transcription-polymerase chain reaction |
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| | SEC, sinusoidal endothelial cell |
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| | TGF-β, transforming growth factor β |
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| | thrombospondin |
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| | TNF-α, tumour necrosis factor α |
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| | transforming growth factor |
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| | TSP, thrombospondin |
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| | tumour necrosis factor |
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| K10plus-PPN: | 1807567753 |
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| Verknüpfungen: | → Zeitschrift |
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Thrombospondin 1 acts as a strong promoter of transforming growth factor β effects via two distinct mechanisms in hepatic stellate cells / Breitkopf-Heinlein, Katja [VerfasserIn]; April 14, 2005 (Online-Ressource)
