Characterization of intracellular pathways leading to coinduction of thrombospondin-1 and TGF-β1 expression in rat hepatic stellate cells
Accumulating evidence has identified Thrombospondin (TSP)-1 as important activator of latent TGF-β. Since little is known about signal transduction pathways regulating TSP expression in liver, we investigated cytokine-mediated upregulation of TSP-1 and TGF-β1 in primary rat hepatic stellate cells (H...
Gespeichert in:
| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2005
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| In: |
Growth factors
Year: 2005, Jahrgang: 23, Heft: 2, Pages: 77-85 |
| ISSN: | 1029-2292 |
| DOI: | 10.1080/08977190500095980 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/08977190500095980
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| Verfasserangaben: | Katja Breitkopf, Iris Sawitza & Axel M. Gressner |
MARC
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| 520 | |a Accumulating evidence has identified Thrombospondin (TSP)-1 as important activator of latent TGF-β. Since little is known about signal transduction pathways regulating TSP expression in liver, we investigated cytokine-mediated upregulation of TSP-1 and TGF-β1 in primary rat hepatic stellate cells (HSC). PDGF-BB and TNF-α rapidly coinduce mRNA levels of TSP-1 and TGF-β1. Interestingly, blockade of basal Erk activity by synthetic Erk-binding peptides also leads to strong induction of both mRNA transcripts in non-stimulated cells. We show that PDGF-BB induces TSP-1 and TGF-β1 via the src kinase pathway whereas TNF-α utilizes the MAPK/Erk pathway. However, especially TSP-1 induction by both cytokines involves a pathway, which depends to a certain extent on PI3 kinase activity.In summary the data illustrate specific pathways activated by PDGF-BB and TNF-α in HSC giving new insights into the tightly controlled mechanisms regulating TSP-1 and TGF-β1 expression in these cells. | ||
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