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

Am J Physiol. 1997 Feb;272(2 Pt 1):G281-8. doi: 10.1152/ajpgi.1997.272.2.G281.


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-kappaB (NF-kappaB) 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-kappaB 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Immunohistochemistry
  • Liver / enzymology*
  • Liver / pathology
  • Liver Cirrhosis, Experimental / enzymology
  • Liver Cirrhosis, Experimental / etiology*
  • Liver Cirrhosis, Experimental / pathology
  • NF-kappa B / physiology*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Transglutaminases / genetics
  • Transglutaminases / metabolism
  • Transglutaminases / physiology*


  • NF-kappa B
  • RNA, Messenger
  • Transglutaminases