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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 272 |
| Issue number | 2 35-2 |
| State | Published - Feb 1997 |
| Externally published | Yes |
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Keywords
- cirrhosis
- fibrosis
- gene regulation
- liver injury
ASJC Scopus subject areas
- Gastroenterology
- Physiology
- Physiology (medical)
Cite this
A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-κB. / Mirza, Ahmed; Liu, Shu Ling; Frizell, Eduardo; Zhu, Jianling; Maddukuri, Sivar; Martinez, José; Davies, Peter; Schwarting, Roland; Norton, Pamela; Zern, Mark A.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 272, No. 2 35-2, 02.1997.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-κB
AU - Mirza, Ahmed
AU - Liu, Shu Ling
AU - Frizell, Eduardo
AU - Zhu, Jianling
AU - Maddukuri, Sivar
AU - Martinez, José
AU - Davies, Peter
AU - Schwarting, Roland
AU - Norton, Pamela
AU - Zern, Mark A
PY - 1997/2
Y1 - 1997/2
N2 - 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.
AB - 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.
KW - cirrhosis
KW - fibrosis
KW - gene regulation
KW - liver injury
UR - http://www.scopus.com/inward/record.url?scp=0030900790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030900790&partnerID=8YFLogxK
M3 - Article
C2 - 9124352
AN - SCOPUS:0030900790
VL - 272
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 2 35-2
ER -