Author： Breitkopf Katja Sawitza Iris Gressner Axel M.
Publisher： Informa Healthcare
ISSN： 0897-7194
Source： Growth Factors, Vol.23, Iss.2, 2005-06, pp. : 77-85
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Abstract
Accumulating evidence has identified Thrombospondin (TSP)-1 as important activator of latent TGF-ß. Since little is known about signal transduction pathways regulating TSP expression in liver, we investigated cytokine-mediated upregulation of TSP-1 and TGF-ß1 in primary rat hepatic stellate cells (HSC). PDGF-BB and TNF-a rapidly coinduce mRNA levels of TSP-1 and TGF-ß1. 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-ß1 via the src kinase pathway whereas TNF-a 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-a in HSC giving new insights into the tightly controlled mechanisms regulating TSP-1 and TGF-ß1 expression in these cells.
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