NF-κB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis

• DOI: 10.1016/j.tox.2008.01.009
• Publication Date: 2008-01-21T12:31:31Z
• Authors: Ching-Shyang Chen; Chih-Hsiung Wu; Yen-Chun Lai; Wen-Sen Lee; Hsiu-Min Chen; Rong-Jane Chen; Li-Ching Chen; Yuan-Soon Ho; Ying-Jan Wang
• Keywords: Mitogen-Activated Protein Kinase 1; 0303 health sciences; Mitogen-Activated Protein Kinase 3; Dose-Response Relationship, Drug; Ethanol; NF-kappa B; Liver Cirrhosis, Experimental; Gene Expression Regulation, Enzymologic; Propolis; Rats; Disease Models, Animal; 03 medical and health sciences; Anti-Infective Agents; GTP-Binding Proteins; Cell Line, Tumor; Flavanones; Hepatocytes; Animals; Humans; Protein Glutamine gamma Glutamyltransferase 2; RNA, Messenger; Enzyme Inhibitors

The increased expression and cross-linking activity of tissue transglutaminase (tTG) have been demonstrated in acute liver injury and fibrosis. We focused on the molecular mechanisms that contribute to ethanol-induced tTG expression and investigated the efficacy of propolis components in preventing both the tTG expression in vitro and fibrogenesis in vivo. We demonstrate herein that both ERK1/2 and PI3K/Akt pathways can regulate the effects of ethanol on NF-kappaB-dependent transcription and these signaling pathways may be involved in activation of ethanol-mediated tTG expression. We also found that administration of pinocembrin (PIN), one of the major components of propolis, inhibited tTG activation and significantly prevented the development of thioacetamide (TAA)-induced liver cirrhosis. The present study suggests that tTG may be an important member of the cascade of factors necessary for ethanol-induced liver fibrogenesis and PIN could serve as an anti-fibrogenic agent.