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...

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Bibliographic Details
Main Authors: Breitkopf-Heinlein, Katja (Author) , Sawitza, Iris (Author) , Gressner, Axel M. (Author)
Format: Article (Journal)
Language:English
Published: 2005
In: Growth factors
Year: 2005, Volume: 23, Issue: 2, Pages: 77-85
ISSN:1029-2292
DOI:10.1080/08977190500095980
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/08977190500095980
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Author Notes:Katja Breitkopf, Iris Sawitza & Axel M. Gressner
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Summary: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.
Item Description:Elektronische Reproduktion der Druck-Ausgabe
Published online: 11 Jul 2009
Gesehen am 23.06.2022
Physical Description:Online Resource
ISSN:1029-2292
DOI:10.1080/08977190500095980