NF-κB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis
- 作者：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
- 关键词：Tissue transglutaminase ; NF-κ ; B ; Ethanol ; Fibrogenesis ; Propolis
- 刊名：Toxicology
- 出版年：2008
- 期刊代码：47_0300483x
- 类别：pha
- 出版时间：18 April 2008
- 卷：246
- 期：2-3
- 页码：148-157
- 文件大小：1266 K
摘要
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-κB-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.