Thrombospondin 1 acts as a strong promoter of transforming growth factor β effects via two distinct mechanisms in hepatic stellate cells
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...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 14, 2005
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| In: |
Gut
Year: 2005, Jahrgang: 54, Heft: 5, Pages: 673-681 |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gut.2004.042911 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/gut.2004.042911 Verlag, lizenzpflichtig, Volltext: https://gut.bmj.com/content/54/5/673 
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| Verfasserangaben: | K. Breitkopf, I. Sawitza, J.H. Westhoff, L. Wickert, S. Dooley, A.M. Gressner |
| Zusammenfassung: | 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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| Beschreibung: | Gesehen am 23.06.2022 |
| Beschreibung: | Online Resource |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gut.2004.042911 |