Abstract:
BACKGROUND & AIMS:Inflammatory gene expression plays a pathological role in acute and chronic hepatic inflammation, yet, inflammation also promotes liver repair by inducing protective mechanisms to limit collateral tissue damage by priming hepatocytes for proliferation. Early growth response (Egr)-1, a transcription factor that regulates inflammatory gene expression, plays a pathological role in many animal models of acute and chronic inflammatory disease. Here, we tested the hypothesis that Egr-1 is beneficial after toxic liver injury. METHODS:Acute liver injury was induced in wild-type and egr-1-/- mice by a single injection of carbon tetrachloride (CCl(4)). Liver injury, inflammatory, and hepatoprotective gene expression and signaling events were measured 18, 48, and 72 h after CCl(4) administration. RESULTS:Peak liver injury was greater in egr-1-/- mice compared to wild-type mice. Enhanced injury in egr-1-/- mice was associated with reduced tumor necrosis factor (TNF)alpha mRNA and protein expression, reduced Akt phosphorylation and nuclear localization of NFkappaB-p65 in nuclei of cells in the hepatic sinusoid. Expression of inducible nitric oxide synthase and cyclooxygenase-2, TNFalpha-regulated genes that have hepatoprotective function, was attenuated in egr-1-/- mice compared to wild-type mice. Although plasma interleukin (IL)-6 protein and hepatic accumulation of IL-6, glycoprotein 130, and IL-6 receptor alpha mRNA in wild-type and egr-1-/- mice were equivalent, signal transducer and activator of transcription 3 phosphorylation was attenuated in egr-1-/- mice and associated with reduced oncostatin M expression. CONCLUSIONS:In contrast to its role in inflammation-mediated tissue injury in other models, Egr-1 expression promotes protection in the liver after CCl(4) exposure.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Pritchard MT,Cohen JI,Roychowdhury S,Pratt BT,Nagy LEdoi
10.1016/j.jhep.2010.04.017subject
Has Abstractpub_date
2010-10-01 00:00:00pages
655-62issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(10)00526-Xjournal_volume
53pub_type
杂志文章abstract:BACKGROUND & AIMS:The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this stu...
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更新日期:1991-01-01 00:00:00
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abstract::To define the epidemiologic and clinical significance of delta infection in the Naples area, we sought anti-delta antibodies in all cases of HBV-associated liver diseases, hospitalized in our department during 1983 (234 acute hepatitis, 9 of which fulminant; 51 chronic hepatitis; 32 cirrhosis; 19 hepatocarcinomas) and...
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doi:10.1016/s0168-8278(98)80316-4
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更新日期:1994-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-03-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.11.012
更新日期:2012-04-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jhep.2007.02.018
更新日期:2007-07-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.01.051
更新日期:2011-11-01 00:00:00
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更新日期:1997-05-01 00:00:00
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pub_type: 临床试验,杂志文章
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pub_type: 临床试验,杂志文章
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更新日期:2006-10-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.07.031
更新日期:2012-12-01 00:00:00
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更新日期:2000-09-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
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更新日期:1994-10-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:2002-07-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:1994-07-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:1986-01-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:2018-11-01 00:00:00
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更新日期:2000-01-01 00:00:00