Abstract:
BACKGROUND & AIMS:Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. METHODS:We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2(-/-) mice. RESULTS:Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2(-/-) mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2(-/-) mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. CONCLUSIONS:Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Wang L,Hartmann P,Haimerl M,Bathena SP,Sjöwall C,Almer S,Alnouti Y,Hofmann AF,Schnabl Bdoi
10.1016/j.jhep.2014.02.012subject
Has Abstractpub_date
2014-06-01 00:00:00pages
1259-67issue
6eissn
0168-8278issn
1600-0641pii
S0168-8278(14)00118-4journal_volume
60pub_type
杂志文章abstract:BACKGROUND/AIMS:We previously reported that the populations of lymphocytes and the expression of activated antigens in human sinusoidal mononuclear cells were different from those in peripheral blood mononuclear cells. Attempts to culture these cells for further study failed because they died rapidly under standard cul...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80016-5
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND/AIMS:Liver growth factor (LGF) is a hepatic mitogen, however, the hepatic stimulation pathway remains to be characterized. The aim of this study was to determine whether tumor necrosis factor alpha (TNF-alpha) stimulation constitutes a step in the mitogenic pathway of LGF. METHODS:Rats were injected with 4....
journal_title:Journal of hepatology
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更新日期:2017-09-01 00:00:00
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journal_title:Journal of hepatology
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doi:10.1016/j.jhep.2003.10.017
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND & AIMS:We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. METHODS:Longitudinal data collection included s...
journal_title:Journal of hepatology
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doi:10.1016/j.jhep.2013.08.014
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND & AIM:Virus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Herein, we dissected the impact of locally induced IFN-I responses...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.11.029
更新日期:2018-04-01 00:00:00
abstract::In recent years a new concept of the mechanism of hepatic fatty acid uptake has been described. It was shown that this major class of energy yielding substrates enters hepatocytes by a carrier-mediated uptake system. After the dissociation of the fatty acid-albumin complex at the sinusoidal liver cell plasma membrane,...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/0168-8278(89)90148-7
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND/AIM:Chronic rejection is an important cause of graft loss following liver transplantation. A number of risk factors for chronic rejection have been identified previously, albeit inconsistently. These include cytomegalovirus infection detected by a number of different techniques, including immunohistochemical...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80294-3
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND/AIMS:The use of cell lines in bioartificial liver support systems (BALSS) to treat fulminant hepatic failure (FHF) is hindered by their reduced metabolic functions, which could be further decreased by the patient's serum/plasma. Hence, the aim of this study was to (i) test the effect of the FHF serum on C3A ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.06.012
更新日期:2004-10-01 00:00:00
abstract::One hundred and eight patients with cirrhosis (23 grade A, 46 grade B and 39 grade C, according to Pugh's classification) underwent hemodynamic studies and plasma catecholamine concentration measurements. Blood samples were withdrawn from the pulmonary artery (n = 108), the hepatic vein (n = 108), the azygos vein (n =...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90810-x
更新日期:1991-09-01 00:00:00
abstract:BACKGROUND/AIMS:Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent eff...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00172-1
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor,...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2008.12.023
更新日期:2009-05-01 00:00:00
abstract::The risk of HCV transmission by blood and blood products has been greatly reduced since the early 1980's. Selection of non-remunerated donors, donor selection to prevent HIV transmission, initial surrogate testing in some regions, and introduction of anti-HCV testing have all contributed to this. ALT surrogate testing...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(99)80384-5
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND/AIM:Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day. METHODS:Twe...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-08-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.011
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS:A total of 151 patients r...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80214-1
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND & AIMS:Receptor mediated cell death through the activation of caspases has been identified as an important mechanism to control life and death in various tissues and is thus crucial for the maintenance of liver tissue homeostasis. Here we investigated how caspase 8 (Casp8) differentially regulates immune-med...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.07.026
更新日期:2013-12-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to increase further in the next years. In spite of the advances of classical therapies, such as surgery, transplantation, use of radiofrequency and transarterial embolization, the prognosis of this neoplasm ...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2013.09.009
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND & AIMS:p53 mutations occur frequently in human HCC. Activation of the mammalian target of rapamycin (mTOR) pathway is also associated with HCC. However, it is still unknown whether these changes together initiate HCC and can be targeted as a potential therapeutic strategy. METHODS:We generated mouse models ...
journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
abstract:BACKGROUND/AIMS:This study aimed to determine whether there is an increased infectious risk following liver biopsy in liver transplant patients with choledochojejunostomy. METHODS:We evaluated the incidence of liver-biopsy-related sepsis in a consecutive series of 27 patients who underwent choledochojejunostomy, eithe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80012-2
更新日期:1996-03-01 00:00:00
abstract::This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.01.037
更新日期:2015-02-10 00:00:00
abstract:BACKGROUND/AIMS:Venous hyporesponsiveness in portal hypertension has been reported previously by us. The present study was undertaken to investigate possible changes of phosphoinositide signal transduction pathway in the portal veins from portal hypertensive rats METHODS:Portal hypertension was induced by partial port...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80055-4
更新日期:1997-02-01 00:00:00
abstract::Calcium concentrations in pig livers were serially estimated following ischemia-reperfusion. Ischemia was produced by clamping the hepatic artery and the portal vein for 90 min (Group 1, n = 6) or for 180 min (Group 2, n = 6) during temporary side-to-side portacaval shunt performed before the induction of ischemia. Al...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80140-0
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND/AIMS:In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. METHODS:We conducted an epidemiological investigat...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.06.012
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND/AIMS:Catabolism is associated with decreased serum concentrations of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 associated with elevated IGFBP-3 protease activity and increased concentrations of IGFBP-1 and -4. The effects of the acute phase mediators interleu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00170-2
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND & AIMS:Genetic variants of patatin-like phospholipase domain-containing 3 (PNPLA3) and diabetes are associated with liver disease severity, in patients with chronic hepatitis C (CHC) infection. We aimed at exploring their interaction in determining hepatitis C virus (HCV)-related liver fibrosis. METHODS:The...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.10.011
更新日期:2015-03-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80546-9
更新日期:1987-06-01 00:00:00
abstract::The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units unti...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1990-01-01 00:00:00
abstract:BACKGROUND/AIMS:Some patients chronically infected with the hepatitis C virus (HCV) have persistently normal alanine aminotransferase (ALT) levels while progressive liver damage is observed histologically. In the present study, we compared the rate of proliferation, apoptosis, and necrosis in liver biopsy specimens of ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1034/j.1600-0641.2000.033004640.x
更新日期:2000-10-01 00:00:00
abstract::It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80531-8
更新日期:1993-01-01 00:00:00