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 gallstones, with particular interest in the role of phosphate ion, a common food additive and preservative. METHODS:We focused on claudin-3 (Cldn3), a paracellular barrier-forming tight junction protein whose expression in mouse liver decreases with age. Since Cldn3-knockout mice exhibited gallstone diseases, we used them to assess the causal relationship between paracellular phosphate ion permeability and the core formation of cholesterol gallstones. RESULTS:In the liver of Cldn3-knockout mice, the paracellular phosphate ion permeability through hepatic tight junctions was significantly increased, resulting in calcium phosphate core formation. Cholesterol overdose caused cholesterol gallstone disease in these mice. CONCLUSION:We revealed that in the hepatobiliary system, Cldn3 functions as a paracellular barrier for phosphate ions, to help maintain biliary ion homeostasis. We provide in vivo evidence that elevated phosphate ion concentrations play a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease under cholesterol overdose. LAY SUMMARY:Herein, we reveal a new mechanism for cholesterol gallstone formation, in which increased paracellular phosphate ion permeability across hepatobiliary epithelia causes calcium phosphate core formation and cholesterol gallstones. Thus, altered phosphate ion metabolism under cholesterol overdose plays a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Tanaka H,Imasato M,Yamazaki Y,Matsumoto K,Kunimoto K,Delpierre J,Meyer K,Zerial M,Kitamura N,Watanabe M,Tamura A,Tsukita Sdoi
10.1016/j.jhep.2018.08.025subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1308-1316issue
6eissn
0168-8278issn
1600-0641pii
S0168-8278(18)32374-2journal_volume
69pub_type
杂志文章abstract:BACKGROUND/AIMS:Hepcidin is a liver-expressed peptide which plays an important role in the regulation of iron metabolism. It is a negative regulator of iron absorption and release of iron from cells. The aims of this study were to analyse the expression and localisation of prohepcidin in liver and cell lines. METHODS:...
journal_title:Journal of hepatology
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pub_type: 临床试验,杂志文章,随机对照试验
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abstract:BACKGROUND/AIMS:Oxidative DNA damage, identifiable in the formation of 8-hydroxydeoxyguanosine (8-OHdG), is relevant in the mutagenesis/carcinogenesis process. The aim of this study was to assess 8-OHdG levels in patients with hepatitis C virus (HCV) infection in relation to extent of liver damage and HCV genotype. ME...
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abstract:BACKGROUND & AIMS:The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. METHODS:In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained vi...
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journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
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abstract:BACKGROUND/AIM:A low-titered hepatitis B virus infection without immunological markers was identified in a prospective study in the serum of a kidney transplant recipient by PCR. The aim of this study was to analyze HBV genomes and their biological significance. METHODS:The genome was amplified in two overlapping frag...
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pub_type: 杂志文章
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更新日期:2000-11-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2015.03.008
更新日期:2015-07-01 00:00:00
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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
doi:10.1016/j.jhep.2007.08.020
更新日期:2008-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0168-8278(92)90153-g
更新日期:1992-03-01 00:00:00
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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(98)80253-5
更新日期:1998-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0168-8278(95)80432-3
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND & AIMS:Low levels of toll-like receptor 3 (TLR3) in patients with hepatocellular carcinoma (HCC) are associated with poor prognosis, primarily owing to the loss of inflammatory signaling and subsequent lack of immune cell recruitment to the liver. Herein, we explore the role of TLR3-triggered apoptosis in HC...
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doi:10.1016/j.jhep.2013.09.009
更新日期:2014-02-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.04.015
更新日期:2004-08-01 00:00:00
abstract::Drug induced hepatotoxicity has been reported infrequently with sulfonylureas. For glimepiride, a second-generation sulfonylurea there is no report of hepatotoxicity in English literature. A patient with non-insulin-dependent diabetes mellitus who developed cholestatic liver injury soon after initiation of glimepiride...
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doi:10.1016/j.jhep.2005.02.011
更新日期:2005-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00189-2
更新日期:2003-08-01 00:00:00
abstract:BACKGROUND/AIMS:In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis. METHODS:We assessed the gene...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(96)80140-1
更新日期:1996-05-01 00:00:00
abstract::HCV infection is a global health problem that affects 170 million people worldwide. The severity of the disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma (HCC). Recently, the standard of care for genotype 1 patients has greatly improved with the addition of protease inhibitor...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2012.05.016
更新日期:2012-11-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.11.011
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND/AIMS:Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic integrity and regenerative activity. METHODS:Expression of IL-15 a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.04.008
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and obesity are epidemiologically correlated with each other but the causal inter-relationships between them remain incompletely understood. We aimed to explore the causal relationships between the 3 diseases. METHODS:Using both UK Biob...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.03.006
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND/AIMS:We aimed to compare the anti-hepatitis C virus reactivity in confirmatory assays (RIBA 3.0 Ortho Diagnostic and INNO-LIA HCV Ab III Innogenetics) among patients infected with different hepatitis C virus genotypes, with or without cryoglobulinemia, and in patients treated with interferon. METHODS:One hu...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(98)80275-4
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND/AIMS:Reactive oxygen species (ROS), such as H2O2, are implicated in normal and pathological liver function. However, due to the lack of suitable in vivo models of ROS generation the (patho) physiological relevance of H2O2 remains controversial. METHODS:We established a novel model of sustained hepatic H2O2 ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.09.025
更新日期:2007-03-01 00:00:00