Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cholangitis
| Project/Area Number |
26460416
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Research Collaborator |
SATO Yasunori
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 原発性胆汁性胆管炎 / 慢性非化膿性破壊性胆管炎 / 代謝 / 原発性胆汁性肝硬変 / ピルビン酸脱水酵素複合体 / 解糖系 / 脂肪酸代謝系 / エストロゲン関連受容体 / ピルビン酸脱水素酵素複合体 |
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| Outline of Final Research Achievements |
Primary biliary cholangitis (cirrhosis) (PBC) is characterized by chronic nonsuppurative destructive cholangitis (CNSDC). Estrogen-related receptor-α (ERRα) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Moreover, the PGC-1α/ERRα axis interrupts glycolytic metabolism through the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which functionally inhibits PDC-E1α and stimulates fatty acid oxidation. In this study, we clarified that, in CNSDC of PBC, the activation of the ERRα/PGC-1α axis was exclusively observed, suggesting the interference of PDC-related glycolytic function and the induction of the fatty acid degradation system. Moreover, upregulation of oxidative stress, proapoptotic molecules, and apopsosis are shown in CNSDC. These suggest that the switching of the cellular energy system is possibly associated with the pathogenesis of CNSDC in PBC.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Pathological Findings of Nonalcoholic Steatohepatitis and Nonalcoholic Fatty Liver Disease.2017
Author(s)
Sakamoto M, Tsujikawa H, Effendi K, Ojima H, Harada K, Zen Y, Kondo F, Nakano M, Kage M, Sumida Y, Hashimoto E, Yamada G, Okanoue T, Koike K.
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Journal Title
Pathology International
Volume: 67
Issue: 1
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hydrophobic bile acids suppress expression of AE2 in biliary epithelial cells and induce bile duct inflammation in primary biliary cholangitis.2016
Author(s)
Hisamoto S, Shimoda S, Harada K, Iwasaka S, Onohara S, Chong Y, Nakamura M, Bekki Y, Yoshizumi T, Ikegami T, Maehara Y, He XS, Gershwin ME, Akashi K.
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Journal Title
J Autoimmun.
Volume: 75
Pages: 150-160
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pathological Findings of NASH and NAFLD2016
Author(s)
Effendi K, Harada K, Hashimoto E, Kage M, Koike K, Kondo F, Nakano M, Ojima H,Okanoue T, Sakamoto M, Sumida Y, Tsujikawa H, Yamada G, Zen Y.
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Journal Title
Hepatol Res.
Volume: ー
Issue: 1
Pages: 3-10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inflammatory Features of Pancreatic Cancer Highlighted byMonocytes/Macrophages and CD4+ T cells with Clinical Impact.2015
Author(s)
Komura T, Sakai Y, Harada K, Kawaguchi K, Takabatake H, Kitagawa H, Wada T, Honda M, Ohta T, Nakanuma Y, Kaneko S.
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Journal Title
Cancer Sci.
Volume: 106(6)
Issue: 6
Pages: 672-86
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gadd34 regulates liver regeneration in hepatic steatosis.2015
Author(s)
Inaba Y, Furutani T, Kimura K, Watanabe H, Haga S, Kido Y, Yamamoto Y, Harada K, Kaneko S, Oyadomari S, Ozaki M, Kasuga M, Inoue H.
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Journal Title
Hepatology
Volume: 61(4)
Issue: 4
Pages: 1343-1356
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Autoantibody status and histological variables influence biochemical rewsponse to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis2015
Author(s)
Minoru nakamura, Hisayoshi Kondo, Atsushi Tanaka, Atsumasa Komori, Masahiro Ito, Kazuhide Yamamoto, Hiromasa Ohira, Mikio Zeniya, Etsuko Hasimoto, Masao Honda,Shuichi Kaneko, Yoshiyuki Ueno, Kentaro Kikuchi, Shinji Shimoda, Kenichi Harada ,et al.
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Journal Title
Hepatol Res.
Volume: 45
Pages: 846-855
Related Report
Peer Reviewed
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[Journal Article] Natural killer cells regulate T cell immune responses in primary biliary cirrhosis.2015
Author(s)
Shimoda S, Hisamoto S, Harada K, Iwasaka S, Chong Y, Nakamura M, Bekki Y, Yoshizumi T, Shirabe K, Ikegami T, Maehara Y, He XS, Gershwin ME, Akashi K.
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Journal Title
Hepatology.
Volume: 62
Issue: 6
Pages: 1817-1827
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis.2014
Author(s)
Harada K, Kakuda Y, Sato Y, Ikeda H, Shimoda S, Yamamoto Y, Inoue H, Ohta H, Kasashima S, Kawashima A, Nakanuma Y.
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Journal Title
J Clin Pathol
Volume: 67(5)
Issue: 5
Pages: 396-402
DOI
NAID
Related Report
Peer Reviewed / Open Access
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