Pharmacological application of caffeine inhibits TGF-β-stimulated connective tissue growth factor (CTGF/CCN2) expression in hepatocytes via PPARγ and Smad2/3-dependent pathways

Introduction: Several epidemiological studies suggest that coffee drinking is an environmental risk modulator of hepatic fibrogenesis. 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 revers…