A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-κB

Ahmed Mirza, Shu Ling Liu, Eduardo Frizell, Jianling Zhu, Sivar Maddukuri, José Martinez, Peter Davies, Roland Schwarting, Pamela Norton, Mark A Zern

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

This study was undertaken to delineate a possible role for tissue transglutaminase (tTG), an enzyme that catalyzes protein cross-linking, in hepatic fibrogenesis. Rats were treated with CCl4 solution and then killed at different stages of liver injury and fibrogenesis. Liver tTG mRNA levels were markedly increased as early as 6 h after the first injection, peaked at 4 days and 1 wk, and remained increased for 8 wk. The enzymatic activity of tTG was increased in livers of rats treated with CCl4, in a fashion that paralleled the Northern blot results. Cell isolation experiments indicated that all hepatic cell types synthesize tTG mRNA. Increased binding to the nuclear factor-κB (NF-κB) motif of the tTG promoter was found in the nuclear extracts prepared from CCl4-treated samples. These data demonstrate an increase in tTG gene expression during hepatic injury and fibrosis, suggesting a possible role for this enzyme in stabilizing the fibrotic bands during hepatic fibrogenesis. Moreover, increased NF-κB binding to the tTG promoter may represent one of the mechanisms by which cell injury induces tTG transcription and thus potentiates the process of fibrogenesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume272
Issue number2 35-2
StatePublished - Feb 1997
Externally publishedYes

Keywords

  • cirrhosis
  • fibrosis
  • gene regulation
  • liver injury

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

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    Mirza, A., Liu, S. L., Frizell, E., Zhu, J., Maddukuri, S., Martinez, J., Davies, P., Schwarting, R., Norton, P., & Zern, M. A. (1997). A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-κB. American Journal of Physiology - Gastrointestinal and Liver Physiology, 272(2 35-2).