BACKGROUND/AIMS: Epidemiological studies suggest that coffee drinking is inversely
correlated with the risk of development of liver fibrosis but the molecular basis is unknown.
METHODS: We investigated the pharmacological mechanisms involved in caffeine-
dependent regulation of CTGF expression, an important modulator protein of fibrogenic TGF-
β, in rat hepatocytes using Western-blot, co-immunoprecipitations, reporter-gene-assays
and ELISAs. RESULTS: It is demonstrated that caffeine, similar to 8-Br-cAMP, suppresses�…

Methods: We investigated the molecular events involved in caffeine-induced inhibition of
TGF-β dependent and independent CTGF-expression in primary rat hepatocytes by western-
blot, co-immunoprecipitations, luminometric-and reporter-gene-assays and ELISA. Results:
We demonstrate that Caffeine increases cAMP-levels in hepatocytes. Administration of 8-Br-
cAMP and caffeine suppresses CTGF-expression, Smad2 protein-levels and Smad1/3-
phosphorylation in hepatocytes which can be reversed by inhibition of the proteasome�…