| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
modulates expression of the tissue transglutaminase
gene in liver cells
1 Department of Medicine and
the Department of Pathology, Anatomy, and Cell Biology, Thomas
Jefferson University, Philadelphia, Pennsylvania 19107;
2 Department of Integrative
Biology,
One of several
postulated roles for tissue transglutaminase (tTG) is the stabilization
and assembly of extracellular matrix via peptide cross-linking. We
previously determined that tTG activity increased in an animal model of
hepatic fibrogenesis and in human liver disease. To further study the
role of tTG in liver disease, we initiated investigations into the
effect of a proinflammatory mediator, tumor necrosis factor (TNF)-
,
on tTG activity in cultured liver cells. Treatment of human Hep G2
cells with 1 ng/ml TNF- increased
[14C]putrescine
cross-linking to cellular proteins. An increase in tTG mRNA content was
observed 1 h after addition of TNF-, and levels of tTG mRNA remained
elevated after 24 h. Hep G2 cells, transiently transfected with a
luciferase reporter containing 1.67 kb of the human tTG promoter,
showed an increase in reporter activity after addition of TNF-. Gel
shift experiments using nuclear extracts from TNF--treated cells and
oligonucleotides containing the tTG nuclear factor (NF)-
B motif
revealed increased binding, concordant with mRNA data. Transient
transfections with a truncated reporter construct lacking the tTG
NF-B sequence showed an attenuated response to TNF- treatment.
Similar responses were seen in stably transfected HeLa cells. Primary
hepatocytes isolated from a trangenic mouse line containing the mouse
tTG promoter driving the 
-galactosidase reporter, show similar
time-dependent increases in promoter activity when treated with
TNF-. Furthermore, Hep G2 cells are incapable of upmodulating tTG
promoter reporter activity in the presence of TNF- when those cells
overexpress a transdominant, negative mutant NF-B subunit. Because
TNF- expression is upregulated in hepatic inflammation, the data
suggest TNF--mediated increases in tTG expression may play an
important role in the process of hepatic fibrogenesis.
transcriptional regulation; nuclear factor-B; hepatocytes
This article has been cited by other articles:
|
|
 |
|
  C Esposito, F Paparo, I Caputo, M Rossi, M Maglio, D Sblattero, T Not, R Porta, S Auricchio, R Marzari, et al. Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ Gut, August 1, 2002; 51(2): 177 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Lu, A. Strohecker, and J.-h. Ou Post-translational Modification of the Hepatitis C Virus Core Protein by Tissue Transglutaminase J. Biol. Chem., December 14, 2001; 276(51): 47993 - 47999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Auld, H. Ritchie, L. A. Robbie, and N. A. Booth Thrombin Upregulates Tissue Transglutaminase in Endothelial Cells: A Potential Role for Tissue Transglutaminase in Stability of Atherosclerotic Plaque Arterioscler. Thromb. Vasc. Biol., October 1, 2001; 21(10): 1689 - 1694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. P. Uray, P. J. A. Davies, and L. Fésüs Pharmacological Separation of the Expression of Tissue Transglutaminase and Apoptosis after Chemotherapeutic Treatment of HepG2 Cells Mol. Pharmacol., June 1, 2001; 59(6): 1388 - 1394. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. A. Rosado, I. Rosenzweig, S. Harding, and S. O. Sage Tumor necrosis factor-{alpha} inhibits store-mediated Ca2+ entry in the human hepatocellular carcinoma cell line HepG2 Am J Physiol Cell Physiol, June 1, 2001; 280(6): C1636 - C1644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Inada, M. Matsuki, K. Yamada, Y. Morishima, S.-C. Shen, N. Kuramoto, H. Yasuno, K. Takahashi, Y. Miyachi, and K. Yamanishi Facilitated Wound Healing by Activation of the Transglutaminase 1 Gene Am. J. Pathol., December 1, 2000; 157(6): 1875 - 1882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Krig and R. H. Rice TCDD Suppression of Tissue Transglutaminase Stimulation by Retinoids in Malignant Human Keratinocytes Toxicol. Sci., August 1, 2000; 56(2): 357 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. A. HAROON, J. M. HETTASCH, T.-S. LAI, M. W. DEWHIRST, and C. S. GREENBERG Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis FASEB J, October 1, 1999; 13(13): 1787 - 1795. [Abstract] [Full Text]
|
|
|
|
|
|
J. Wu, S.-L. Liu, J.-L. Zhu, P. A. Norton, S. Nojiri, J. B. Hoek, and M. A. Zern Roles of Tissue Transglutaminase in Ethanol-induced Inhibition of Hepatocyte Proliferation and alpha 1-Adrenergic Signal Transduction J. Biol. Chem., July 14, 2000; 275(29): 22213 - 22219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Citron, K. S. SantaCruz, P. J. A. Davies, and B. W. Festoff Intron-Exon Swapping of Transglutaminase mRNA and Neuronal Tau Aggregation in Alzheimer's Disease J. Biol. Chem., January 26, 2001; 276(5): 3295 - 3301. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
