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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Breitkopf, K. et al.

Breitkopf, Sawitza, Gressner,

Characterization of intracellular pathways leading to coinduction of thrombospondin-1 and TGF-beta1 expression in rat hepatic stellate cells.

Accumulating evidence has identified Thrombospondin (TSP)-1 as important activator of latent TGF-beta. Since little is known about signal transduction pathways regulating TSP expression in liver, we investigated cytokine-mediated upregulation of TSP-1 and TGF-beta1 in primary rat hepatic stellate cells (HSC). PDGF-BB and TNF-a rapidly coinduce mRNA levels of TSP-1 and TGF-beta1. 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-beta1 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-beta1 expression in these cells.[1]

References

Characterization of intracellular pathways leading to coinduction of thrombospondin-1 and TGF-beta1 expression in rat hepatic stellate cells. Breitkopf, K., Sawitza, I., Gressner, A.M. Growth Factors (2005) [Pubmed]

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