Inhibitory effect of a soluble transforming growth factor β type II receptor on the activation of rat hepatic stellate cells in primary culture

Transcriptional activation by growth hormone of HNF-6-regulated hepatic genes, a potential mechanism for improved liver repair during biliary injury in mice

“…In support of the possibility of TGFb2R-negative transcriptional regulation by HNF-6, TGFb2R expression and TGF-␤ signaling pathways were upregulated in embryonic liver of HNF-6-null mice (6,28). Our results demonstrating parallel suppression of ␣-SMA expression, a marker for hepatic stellate cells and portal fibroblast-dependent fibrogenesis (10,29,43), thus provide a mechanistic basis for previously seen antifibrotic effects of GH administration in BDL rats (33). It is possible that diminished HNF-6 function in GH-treated liver can alter cross talk between hepatocytes or biliary cells and mesenchymal cells in the form of downregulating the TGFb2R-mediated recruitment pathways for the fibroblastic response by the liver epithelial cells during biliary fibrogenesis.…”

“…7E) which was in turn associated with similar downregulation of ␣-SMA protein expression (Fig. 7E), showing that TGFb2R signaling pathways potentially mediated by hepatocytes and biliary cells in inducing myofibroblastic transdifferentiation of hepatic stellate cells and portal fibroblasts (10,29,43) during fibrogenesis can be suppressed in GH-treated BDL mice, thus providing a mechanism for previously published data showing that GH attenuated fibrosis in cholestatic rats (33).…”

Iron deposition causes oxidative stress, inflammation and fibrosis in carbon tetrachloride-induced liver dysfunction in rats

“…Oxidative stress through generation of ROS plays an important role in the development of liver damage and increases the inflammatory responses which ultimately stimulates the production of pro-fibrogenic mediators and initiate hepatic fibrogenesis (Cui et al, 2003;Galli et al, 2005;Ghiassi-Nejad and Friedman, 2008). In our study, it was found that, administration of CCl4 resulted in a significant depletion of liver GSH accompanied with a significant increase in lipid peroxidation product TBARS as compared to the control group.…”

Dominant-negative soluble PDGF-β receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis

“…16 Further, the beneficial impact of sTbRII was recently demonstrated to have an inhibitory effect on the activation of rat HSC in primary culture resulting from interruption of the TGF-b autocrine signaling-loop. 18 Among other polypeptide growth factors potentially involved in chronic liver inflammation, PDGF has shown to be the most potent mitogen for cultured HSC isolated from rat, mouse, or human liver 3 reflecting the most striking molecular response of HSC to injury. Of the different possible dimeric forms of PDGF, PDGF-BB functions as the strongest stimulator of HSC growth and intracellular signaling with concurrent predominant expression of PDGFreceptor b (or type b) subunits in activated HSC.…”

“…3 Therefore, direct scavenging of PDGF or application of methods allowing targeting to HSC undergoing cellular activation and subsequent transdifferentiation would offer a strategy for the treatment of fibrotic liver diseases. Inspired by the overwhelming literature describing the highly beneficial impact of local or systemic expression of a dominant-negative TGF-b receptor (TbRII) resulting in the reduction of liver fibrogenesis, improved liver function, and inhibition of cellular activation, [16][17][18] we examined the effects of a dominant-negative soluble PDGFRb (sPDGFRb) on hepatic fibrogenesis in culture-activated HSC and in a biliary obstruction model induced by ligature of the common bile duct (BD) in rats.…”