Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/13364
Title: Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258
Authors: Liu, Y
Wen, XM
Lui, ELH
Friedman, SL
Cui, W
Ho, NPS
Li, L
Ye, T 
Fan, ST
Zhang, H
Keywords: Akt
HSC
PDGF
PTK787/ZK22258
TGF-beta 1
Issue Date: 2009
Publisher: Nature Publishing Group
Source: Laboratory investigation, 2009, v. 89, no. 10, p. 1152-1160 How to cite?
Journal: Laboratory Investigation 
Abstract: Stimulation of hepatic stellate cells (HSCs) by platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1) is an essential pathway of proliferation and fibrogenesis, respectively, in liver fibrosis. We provide evidence that PTK787/ZK222584 (PTK/ZK), a potent tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor (VEGFR), significantly inhibits PDGF receptor expression, as well as PDGF-simulated HSC proliferation, migration and phosphorylation of ERK1/2, Akt and p70S6 kinase. Interestingly, PTK/ZK also antagonizes the TGF-beta 1-induced expression of VEGF and VEGFR1. Furthermore, PTK/ZK downregulates TGF-beta receptor expression, which is associated with reduced Akt, ERK and p38MAPK phosphorylation. Furthermore, PDGF-induced TGF-beta 1 expression is inhibited by PTK/ZK. These findings provide evidence that PTK/ZK targets multiple essential pathways of stellate cell activation that provoke proliferation and fibrogenesis. Our study underscores the potential use of PTK/ZK as an antifibrotic drug in chronic liver disease.
URI: http://hdl.handle.net/10397/13364
ISSN: 0023-6837
DOI: 10.1038/labinvest.2009.77
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