2016 Fiscal Year Final Research Report
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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| Keywords | 原発性胆汁性胆管炎 / 慢性非化膿性破壊性胆管炎 / 代謝 |
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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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| Free Research Field |
病理
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