NF-kappaB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis.
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.
Chen
Ching-Shyang
CS
Center of Quality Management and Breast Health Center, Taipei Medical University Hospital, Taipei, Taiwan.
Wu
Chih-Hsiung
CH
Lai
Yen-Chun
YC
Lee
Wen-Sen
WS
Chen
Hsiu-Min
HM
Chen
Rong-Jane
RJ
Chen
Li-Ching
LC
Ho
Yuan-Soon
YS
Wang
Ying-Jan
YJ
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D000431:Ethanol / Q000633:toxicity*; D044950:Flavanones / Q000737:chemistry / Q000627:therapeutic use*; D019204:GTP-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis*; D011429:Propolis / Q000737:chemistry; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D044950:Flavanones; D016328:NF-kappa B; D012333:RNA, Messenger; D000431:Ethanol; C016063:pinocembrin; D011429:Propolis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019204:GTP-Binding Proteins