Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism

Motoyuki Kohjima, Munechika Enjoji, Ryoko Yada, Tsuyoshi Yoshimoto, Tsukasa Nakamura, Kunitaka Fukuizumi, Nobuyoshi Fukushima, Yusuke Murata, Manabu Nakashima, Masaki Kato, Kazuhiro Kotoh, Ken Shirabe, Yoshihiko Maehara, Atsushi Nakajima, Yuichi Nozaki, Akira Honda, Yasushi Matsuzaki, Makoto Nakamuta

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

Background and Aims: Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC. Methods: Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum/tissue choline levels were also measured. OCT1 expression was quantified by genotype (rs683369 and rs622342). Results: Serum choline concentrations were significantly higher in PBC patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC patients than in controls. The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers. Serum cholesterol concentrations and the cholesterol/triglyceride ratio in serum very low density lipoprotein were markedly higher in PBC patients than in controls. In PBC liver, OCT1 protein levels were lower in patients with minor (CG/GG at rs683369 and/or CC at rs622342) than major (CC at rs683369 and AA at rs622342) genotypes of the OCT1 gene. Conclusion: During early stage PBC, hepatocellular choline uptake and PC synthesis become dysregulated. OCT1 genotypes may influence the pathogenesis of PBC.

元の言語英語
ページ(範囲)1095-1102
ページ数8
ジャーナルLiver International
35
発行部数3
DOI
出版物ステータス出版済み - 3 1 2015

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Biliary Liver Cirrhosis
Choline
Phospholipids
Liver
Serum
Cholesterol
Genotype
Phosphatidylcholines
Organic Cation Transporter 1
Triglycerides
Fibric Acids
VLDL Lipoproteins
Bile
Genes
Lipoproteins
Real-Time Polymerase Chain Reaction
Epithelial Cells
Gene Expression
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Hepatology

これを引用

Kohjima, M., Enjoji, M., Yada, R., Yoshimoto, T., Nakamura, T., Fukuizumi, K., ... Nakamuta, M. (2015). Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism. Liver International, 35(3), 1095-1102. https://doi.org/10.1111/liv.12526

Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism. / Kohjima, Motoyuki; Enjoji, Munechika; Yada, Ryoko; Yoshimoto, Tsuyoshi; Nakamura, Tsukasa; Fukuizumi, Kunitaka; Fukushima, Nobuyoshi; Murata, Yusuke; Nakashima, Manabu; Kato, Masaki; Kotoh, Kazuhiro; Shirabe, Ken; Maehara, Yoshihiko; Nakajima, Atsushi; Nozaki, Yuichi; Honda, Akira; Matsuzaki, Yasushi; Nakamuta, Makoto.

:: Liver International, 巻 35, 番号 3, 01.03.2015, p. 1095-1102.

研究成果: ジャーナルへの寄稿記事

Kohjima, M, Enjoji, M, Yada, R, Yoshimoto, T, Nakamura, T, Fukuizumi, K, Fukushima, N, Murata, Y, Nakashima, M, Kato, M, Kotoh, K, Shirabe, K, Maehara, Y, Nakajima, A, Nozaki, Y, Honda, A, Matsuzaki, Y & Nakamuta, M 2015, 'Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism', Liver International, 巻. 35, 番号 3, pp. 1095-1102. https://doi.org/10.1111/liv.12526
Kohjima, Motoyuki ; Enjoji, Munechika ; Yada, Ryoko ; Yoshimoto, Tsuyoshi ; Nakamura, Tsukasa ; Fukuizumi, Kunitaka ; Fukushima, Nobuyoshi ; Murata, Yusuke ; Nakashima, Manabu ; Kato, Masaki ; Kotoh, Kazuhiro ; Shirabe, Ken ; Maehara, Yoshihiko ; Nakajima, Atsushi ; Nozaki, Yuichi ; Honda, Akira ; Matsuzaki, Yasushi ; Nakamuta, Makoto. / Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism. :: Liver International. 2015 ; 巻 35, 番号 3. pp. 1095-1102.
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title = "Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism",
abstract = "Background and Aims: Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC. Methods: Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum/tissue choline levels were also measured. OCT1 expression was quantified by genotype (rs683369 and rs622342). Results: Serum choline concentrations were significantly higher in PBC patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC patients than in controls. The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers. Serum cholesterol concentrations and the cholesterol/triglyceride ratio in serum very low density lipoprotein were markedly higher in PBC patients than in controls. In PBC liver, OCT1 protein levels were lower in patients with minor (CG/GG at rs683369 and/or CC at rs622342) than major (CC at rs683369 and AA at rs622342) genotypes of the OCT1 gene. Conclusion: During early stage PBC, hepatocellular choline uptake and PC synthesis become dysregulated. OCT1 genotypes may influence the pathogenesis of PBC.",
author = "Motoyuki Kohjima and Munechika Enjoji and Ryoko Yada and Tsuyoshi Yoshimoto and Tsukasa Nakamura and Kunitaka Fukuizumi and Nobuyoshi Fukushima and Yusuke Murata and Manabu Nakashima and Masaki Kato and Kazuhiro Kotoh and Ken Shirabe and Yoshihiko Maehara and Atsushi Nakajima and Yuichi Nozaki and Akira Honda and Yasushi Matsuzaki and Makoto Nakamuta",
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T1 - Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism

AU - Kohjima, Motoyuki

AU - Enjoji, Munechika

AU - Yada, Ryoko

AU - Yoshimoto, Tsuyoshi

AU - Nakamura, Tsukasa

AU - Fukuizumi, Kunitaka

AU - Fukushima, Nobuyoshi

AU - Murata, Yusuke

AU - Nakashima, Manabu

AU - Kato, Masaki

AU - Kotoh, Kazuhiro

AU - Shirabe, Ken

AU - Maehara, Yoshihiko

AU - Nakajima, Atsushi

AU - Nozaki, Yuichi

AU - Honda, Akira

AU - Matsuzaki, Yasushi

AU - Nakamuta, Makoto

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Background and Aims: Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC. Methods: Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum/tissue choline levels were also measured. OCT1 expression was quantified by genotype (rs683369 and rs622342). Results: Serum choline concentrations were significantly higher in PBC patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC patients than in controls. The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers. Serum cholesterol concentrations and the cholesterol/triglyceride ratio in serum very low density lipoprotein were markedly higher in PBC patients than in controls. In PBC liver, OCT1 protein levels were lower in patients with minor (CG/GG at rs683369 and/or CC at rs622342) than major (CC at rs683369 and AA at rs622342) genotypes of the OCT1 gene. Conclusion: During early stage PBC, hepatocellular choline uptake and PC synthesis become dysregulated. OCT1 genotypes may influence the pathogenesis of PBC.

AB - Background and Aims: Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC. Methods: Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum/tissue choline levels were also measured. OCT1 expression was quantified by genotype (rs683369 and rs622342). Results: Serum choline concentrations were significantly higher in PBC patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC patients than in controls. The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers. Serum cholesterol concentrations and the cholesterol/triglyceride ratio in serum very low density lipoprotein were markedly higher in PBC patients than in controls. In PBC liver, OCT1 protein levels were lower in patients with minor (CG/GG at rs683369 and/or CC at rs622342) than major (CC at rs683369 and AA at rs622342) genotypes of the OCT1 gene. Conclusion: During early stage PBC, hepatocellular choline uptake and PC synthesis become dysregulated. OCT1 genotypes may influence the pathogenesis of PBC.

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U2 - 10.1111/liv.12526

DO - 10.1111/liv.12526

M3 - Article

VL - 35

SP - 1095

EP - 1102

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 3

ER -