Abstract:
BACKGROUND & AIMS:Hepatic stellate cell (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is involved in HSC activation and in the multifunctional role of these cells during the response to liver injury. METHODS:COUP-TFII expression was evaluated in normal and cirrhotic livers by immunohistochemistry and Western blot. The role of COUP-TFII in HSC was assessed by gain and loss of function transfection experiments and by generation of mice with COUP-TFII deletion in HSC. Molecular changes were determined by gene expression microarray and RT-qPCR. RESULTS:We showed that COUP-TFII is highly expressed in human fibrotic liver and in mouse models of hepatic injury. COUP-TFII expression rapidly increased upon HSC activation and it was associated with the regulation of genes involved in cell motility, proliferation and angiogenesis. Inactivation of COUP-TFII impairs proliferation and invasiveness in activated HSC and COUP-TFII deletion in mice abrogate HSC activation and angiogenesis. Finally, co-culture experiments with HSC and liver sinusoidal endothelial cells (SEC) showed that COUP-TFII expression in HSC influenced SEC migration and tubulogenesis via a hypoxia-independent and nuclear factor kappaB-dependent mechanism. CONCLUSION:This study elucidates a novel transcriptional pathway in HSC that is involved in the acquisition of the proangiogenic phenotype and regulates the paracrine signals between HSC and SEC during hepatic wound healing. LAY SUMMARY:In this study, we identified an important regulator of HSC pathobiology. We showed that the orphan receptor COUP-TFII is an important player in hepatic neoangiogenesis. COUP-TFII expression in HSC controls the crosstalk between HSC and endothelial cells coordinating vascular remodelling during liver injury. TRANSCRIPT PROFILING:ArrayExpress accession E-MTAB-1795.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Ceni E,Mello T,Polvani S,Vasseur-Cognet M,Tarocchi M,Tempesti S,Cavalieri D,Beltrame L,Marroncini G,Pinzani M,Milani S,Galli Adoi
10.1016/j.jhep.2016.11.003subject
Has Abstractpub_date
2017-04-01 00:00:00pages
754-764issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(16)30650-Xjournal_volume
66pub_type
杂志文章abstract::Portal hypertension is the main cause of complications in patients with chronic liver disease. Over the past 25 years, progress in the understanding of the pathophysiology of portal hypertension was followed by the introduction of an effective pharmacological therapy, consisting mainly of treatments aimed at correctin...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2010.03.021
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND & AIMS:Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS:We used wild type mice and m...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.01.006
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abstract::Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80068-9
更新日期:1995-11-01 00:00:00
abstract::This study set out to examine the relative effectiveness and tolerability of 12- versus 24-week courses of thrice weekly intramuscular lymphoblastoid interferon in the treatment of hepatitis B 'e' antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, and to identify pretreatment factors predicting the ou...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(87)80061-2
更新日期:1987-08-01 00:00:00
abstract:BACKGROUND/AIMS:The precise mechanism of formation and significance of Mallory bodies (MBs) are poorly understood. The endoplasmic reticulum (ER) is the organelle responsible for proper folding and elimination of unfolded proteins. Therefore, failure of this function increases defective proteins in the cell. METHODS:W...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.039
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND/AIMS:The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypot...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.026
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND & AIMS:TMC435 is an investigational, once-daily, oral NS3/4A protease inhibitor currently in phase III development for the treatment of hepatitis C virus (HCV) infection. Phase I and II studies in patients infected with HCV genotype 1 have demonstrated that TMC435 is generally well tolerated, has a pharmacok...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2011.12.033
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND & AIMS:FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.11.016
更新日期:2014-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80280-9
更新日期:2000-09-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90937-7
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND & AIMS:Most cholesterol gallstones have a core consisting of inorganic and/or organic calcium salts, although the mechanisms of core formation are poorly understood. We examined whether the paracellular permeability of ions at hepatic tight junctions is involved in the core formation of cholesterol gallstone...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.08.025
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatic steatosis is an important factor in pathogenesis, progression and response to treatment in hepatitis C. We aimed to investigate differences in hepatic lipid composition in liver biopsies from patients with chronic hepatitis C using proton magnetic resonance spectroscopy ((1)H MRS) and to trans...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.10.006
更新日期:2010-01-01 00:00:00
abstract::The liver contributes to immune surveillance against pathogens entering via the gut and is itself influenced by alterations in mucosal immune responses and the microbiome. Mucosal immunity is also implicated in autoimmune liver diseases that associate with inflammatory bowel disease (IBD), and in steatohepatitis where...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2015.12.002
更新日期:2016-05-01 00:00:00
abstract::Induction of the unfolded protein response (UPR) is recognized as central to fatty liver disease (FLD) pathophysiology. This pathway may be a potential therapeutic target for FLD, as well as other diseases. However, fundamental questions as to how UPR contributes to FLD remain unanswered. Conflicting data suggest that...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2012.06.018
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND/AIMS:Vaccination strategies able to induce strong T-cell responses might contribute to eradicate hepatitis C virus (HCV) infection. We previously demonstrated that fusion of an antigen to the extra domain A from fibronectin (EDA) targets the antigen to TLR4-expressing dendritic cells (DC) and improves its im...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.06.005
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND/AIMS:The extracellular matrix plays an essential role in the regulation of cell proliferation in different cell types. However, the regulation of cell cycle control in hepatocytes in response to growth factors and extracellular matrix signals is not well understood. The aims of this study were to investigate...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80401-8
更新日期:2000-03-01 00:00:00
abstract::The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the ...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2014.05.016
更新日期:2014-09-01 00:00:00
abstract::In a follow-up study of 3 years' duration, serum inhibitory factors (SIF) were analysed in 23 patients with a protracted course of viral hepatitis B (PVH) and 12 patients with chronic persistent hepatitis (CPH). Four patients showed a progressive course, developing chronic active hepatitis, and one died of liver failu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80083-1
更新日期:1987-04-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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abstract::The relationship of the endoscopic aspect of esophageal varices, portal quantitative Doppler ultrasound parameters and clinical and biochemical findings was assessed in 149 patients with cirrhosis stratified according to the presence of esophageal varices (n = 115) and the absence of previous bleeding (n = 96). In thi...
journal_title:Journal of hepatology
pub_type: 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:1996-05-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80262-2
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80281-8
更新日期:1993-07-01 00:00:00
abstract::To evaluate the efficacy of recombinant interferon alpha-2b in the treatment of patients with acute post-transfusion hepatitis C, a randomized controlled trial was conducted in 33 acute post-transfusion hepatitis C patients; 16 patients received 3 million units of subcutaneously injected recombinant interferon alpha-2...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(94)80246-7
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND/AIMS:HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis. Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting. METHODS:Pegylated-interferon alpha-2b and ribavirin were administered at...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/j.jhep.2006.10.017
更新日期:2007-03-01 00:00:00
abstract::The presence of HBV-DNA sequences was evaluated in DNA extracted from serum samples, peripheral blood lymphocytes and liver biopsy specimens of five HBsAg/anti-HBe-positive carriers with chronic HDV infection. DNAs were tested by polymerase chain reaction (PCR) amplification technique using two pairs of oligonucleotid...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90032-7
更新日期:1991-01-01 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:BACKGROUND & AIMS:Reactive cholangiocytes acquire a neuroendocrine-like phenotype, with synthesis and local release of neuropeptides and hormones. The mechanism that drives such phenotypical changes is still undefined. Pancreatic Duodenal Homeobox-1 (PDX-1) is a transcription factor required for pancreatic development,...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.022
更新日期:2010-10-01 00:00:00
abstract::Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibil...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2009.05.012
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND & AIMS:This study aimed to identify preoperative magnetic resonance (MR) imaging biomarkers for predicting microvascular invasion (MVI), to determine their diagnostic performance and to evaluate whether they are associated with early recurrence after surgery for single hepatocellular carcinoma (HCC). METHOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.04.024
更新日期:2017-09-01 00:00:00