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

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

A Mirza, S L Liu, E Frizell, J Zhu, S Maddukuri, J Martinez, P Davies, R Schwarting, P Norton and M A Zern
The American journal of physiology, v 272(2 Pt 1), pp G281-G288
Feb 1997
PMID: 9124352

Abstract

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

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Collaboration types
Domestic collaboration
Web of Science research areas
Gastroenterology & Hepatology
Physiology
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