Identification of paraxanthine as the most potent caffeine‐derived inhibitor of connective tissue growth factor expression in liver parenchymal cells

@article{Gressner2009IdentificationOP,
  title={Identification of paraxanthine as the most potent caffeine‐derived inhibitor of connective tissue growth factor expression in liver parenchymal cells},
  author={Olav A. Gressner and Birgit Lahme and Monika Siluschek and Axel M. Gressner},
  journal={Liver International},
  year={2009},
  volume={29},
  url={https://api.semanticscholar.org/CorpusID:32926935}
}
This work was the first to provide evidence that caffeine suppresses transforming growth factor (TGF)‐β dependent and ‐independent CTGF expression in hepatocytes in vitro and in vivo, thus suggesting this xanthine‐alkaloid as a potential therapeutic agent.
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34 Citations
Background Citations
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34 Citations

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42 References

Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats

This investigation conducted an investigation to determine if intraportal vein siRNA injection targeting CTGF inhibits CTGF expression on rat liver in vivo and furthermore whether it protects the liver from liver fibrosis.

Caffeine biotransformation in human hepatocyte lines derived from normal liver tissue.

Caffeine biotransformation was demonstrated in three novel human hepatocyte cell lines established from normal liver tissue and cultured continuously for 19 to 30 months, demonstrating in vitro metabolism of caffeine observed in man in vivo.

Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via PPARgamma and SMAD2/3-dependent pathways.

Profibrogenic transforming growth factor‐β/activin receptor–like kinase 5 signaling via connective tissue growth factor expression in hepatocytes

Evidence is provided for the profibrogenic activity of TGF‐β directed to hepatocytes and mediated via the up‐regulation of CTGF, which can be hindered by an activated activin receptor–like kinase 1 pathway and completely inhibited by T GF‐β antagonist Smad7.

Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes.

Adenosine A2A receptors play a role in the pathogenesis of hepatic cirrhosis

It is demonstrated that hepatic adenosine A2A receptors play an active role in the pathogenesis of hepatic fibrosis, and a novel therapeutic target is suggested in the treatment and prevention of Hepatic cirrhosis.

siRNA-mediated knockdown of connective tissue growth factor prevents N-nitrosodimethylamine-induced hepatic fibrosis in rats

It is demonstrated that CTGF gene silencing through siRNA reduces activation of hepatic stellate cells, prevents the upregulation of CTGF and TGF-β1 gene expression and inhibits accumulation of connective tissue proteins in the liver.

Adenosine reverses a preestablished CCl4‐induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats

Adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery.

Preventive Effects of Acute Inflammation on Liver Cell Necrosis and Inhibition of Heparan Sulphate Synthesis in Hepatocytes

The hepatocytoprotective effect of acute, turpentine-induced inflammation on experimental liver injury, caused by thioacetamide and D-galactosamine, and the pathogenetic potential of heparan sulphate for liver cell necrosis are studied are discussed.

Connective tissue growth factor: what's in a name?

Connective tissue growth factor has emerged as a potential important effector molecule in both physiological and pathological processes and has provided a new target for therapeutic intervention in fibrotic diseases.