RT Journal Article SR Electronic T1 Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 396 OP 402 DO 10.1136/jclinpath-2013-201815 VO 67 IS 5 A1 Harada, Kenichi A1 Kakuda, Yuko A1 Sato, Yasunori A1 Ikeda, Hiroko A1 Shimoda, Shinji A1 Yamamoto, Yasuhiko A1 Inoue, Hiroshi A1 Ohta, Hajime A1 Kasashima, Satomi A1 Kawashima, Atsuhiro A1 Nakanuma, Yasuni YR 2014 UL http://jcp.bmj.com/content/67/5/396.abstract AB Aim Primary biliary cirrhosis (PBC) is characterised by antimitochondrial antibody against the pyruvate dehydrogenase complex (PDC) and chronic non-suppurative destructive cholangitis (CNSDC). Pyruvate oxidation to acetyl-CoA by PDC is a key step in the glycolytic system. Oestrogen-related receptor-α (ERRα) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and Bcl-3. 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 investigated the PGC-1α–ERRα axis to clarify PDC dysfunction in CNSDC of PBC. Methods The expression of PGC-1α, Bcl-3, ERRα, PDK4 and PDC-E1α was examined by immunohistochemistry in liver sections from patients with PBC and controls. The expression of these molecules, the activity of mitochondrial dehydrogenase and PDC, and their alterations by starvation, a treatment used to induce PGC-1α expression, were examined in cultured human biliary epithelial cells (BECs). Results The nuclear expression of PGC-1α, Bcl-3 and ERRα was exclusively observed in CNSDC of PBC. Moreover, the expression of PDK4 and PDC-E1α was enhanced in CNSDC of PBC. In cultured BECs, the amplification of Bcl-3 and PDK4 mRNAs by reverse-transcription-PCR and mitochondrial dehydrogenase activity were markedly increased but PDC activity was decreased according to the upregulation of PGC-1α. Conclusions 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. The switching of the cellular energy system is possibly associated with the pathogenesis of CNSDC in PBC.