A postulated role for tissue transglutaminase in hepatic
fibrogenesis, and its potential regulation by nuclear factor-kb (nf
-kb).
Mirza, Ahmed, Shu-Ling Liu, Eduardo Frizell, Jianling Zhu, Sivar
Maddukuri, Jos[acute]e Martinez, Peter Davies, Roland Schwarting,
Pamela Norton, and Mark A. Zern.
Departments of Medicine and Pathology, Anatomy, and Cell Biology,
Jefferson Medical College, Philadelphia, PA 19107, Departments of
Medicine and Pharmacology, University of Texas-Houston Medical
School, Houston, Texas
APStracts 3:0259G, 1996.
The present 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 carbon
tetrachloride (CC14) solution then sacrificed at different time
points of liver injury and fibrogenesis. Liver tTG mRNA levels were
markedly increased as early as 6 hours after the first injection,
peaked at 4 days and one week, and remained increased for eight
weeks. 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
-kappa B (NF-kB) 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-kB 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.
Received 16 January 1996; accepted in final form 22 November
1996.
APS Manuscript Number G15-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996