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

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)148-157
Number of pages10
JournalToxicology
Volume246
Issue number2-3
DOIs
Publication statusPublished - Apr 18 2008

Fingerprint

Propolis
Ethanol
Liver
Wounds and Injuries
Liver Cirrhosis
Chemical activation
Thioacetamide
Transcription
Phosphatidylinositol 3-Kinases
transglutaminase 2

Keywords

  • Ethanol
  • Fibrogenesis
  • NF-κB
  • Propolis
  • Tissue transglutaminase

ASJC Scopus subject areas

  • Toxicology

Cite this

NF-κB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis. / Chen, Ching Shyang; Wu, Chih Hsiung; Lai, Yen Chun; Lee, Wen Sen; Chen, Hsiu Min; Chen, Rong Jane; Chen, Li Ching; Ho, Yuan Soon; Wang, Ying Jan.

In: Toxicology, Vol. 246, No. 2-3, 18.04.2008, p. 148-157.

Research output: Contribution to journalArticle

Chen, Ching Shyang ; Wu, Chih Hsiung ; Lai, Yen Chun ; Lee, Wen Sen ; Chen, Hsiu Min ; Chen, Rong Jane ; Chen, Li Ching ; Ho, Yuan Soon ; Wang, Ying Jan. / NF-κB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis. In: Toxicology. 2008 ; Vol. 246, No. 2-3. pp. 148-157.
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AU - Lee, Wen Sen

AU - Chen, Hsiu Min

AU - Chen, Rong Jane

AU - Chen, Li Ching

AU - Ho, Yuan Soon

AU - Wang, Ying Jan

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N2 - 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.

AB - 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.

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