{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:27:51Z","timestamp":1764995271307,"version":"3.46.0"},"reference-count":32,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2013,10,24]]},"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>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-\u03b1 (ERR\u03b1) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor \u03b3 coactivator-1\u03b1 (PGC-1\u03b1) and Bcl-3. Moreover, the PGC-1\u03b1\u2013ERR\u03b1 axis interrupts glycolytic metabolism through the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which functionally inhibits PDC-E1\u03b1 and stimulates fatty acid oxidation. In this study, we investigated the PGC-1\u03b1\u2013ERR\u03b1 axis to clarify PDC dysfunction in CNSDC of PBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression of PGC-1\u03b1, Bcl-3, ERR\u03b1, PDK4 and PDC-E1\u03b1 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-1\u03b1 expression, were examined in cultured human biliary epithelial cells (BECs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The nuclear expression of PGC-1\u03b1, Bcl-3 and ERR\u03b1 was exclusively observed in CNSDC of PBC. Moreover, the expression of PDK4 and PDC-E1\u03b1 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-1\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In CNSDC of PBC, the activation of the ERR\u03b1\u2013PGC-1\u03b1 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2013-201815","type":"journal-article","created":{"date-parts":[[2013,11,29]],"date-time":"2013-11-29T20:26:29Z","timestamp":1385756789000},"page":"396-402","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis"],"prefix":"10.1136","volume":"67","author":[{"given":"Kenichi","family":"Harada","sequence":"first","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Kakuda","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunori","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Division of Pathology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Physiology and Metabolism, Brain\/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satomi","family":"Kasashima","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuhiro","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuni","family":"Nakanuma","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2013,11,29]]},"reference":[{"key":"2025120519351414000_67.5.396.1","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/0016-5085(79)90396-2","article-title":"Histometric and serial section observations of the intrahepatic bile ducts in primary biliary cirrhosis","volume":"76","author":"Nakanuma","year":"1979","journal-title":"Gastroenterology"},{"key":"2025120519351414000_67.5.396.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043898"},{"key":"2025120519351414000_67.5.396.3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22042"},{"key":"2025120519351414000_67.5.396.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.08.022"},{"key":"2025120519351414000_67.5.396.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(02)00592-1"},{"key":"2025120519351414000_67.5.396.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.09.021"},{"key":"2025120519351414000_67.5.396.7","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0017"},{"key":"2025120519351414000_67.5.396.8","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01669-08"},{"key":"2025120519351414000_67.5.396.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.08.011"},{"key":"2025120519351414000_67.5.396.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608657200"},{"key":"2025120519351414000_67.5.396.11","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1046\/j.1432-1033.2003.03468.x","article-title":"Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1","volume":"270","author":"Roche","year":"2003","journal-title":"Eur J Biochem"},{"key":"2025120519351414000_67.5.396.12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.5.1835"},{"key":"2025120519351414000_67.5.396.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2009.02500.x"},{"key":"2025120519351414000_67.5.396.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2008.11.007"},{"key":"2025120519351414000_67.5.396.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.proghi.2006.09.001"},{"key":"2025120519351414000_67.5.396.16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20379"},{"key":"2025120519351414000_67.5.396.17","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.3.642"},{"key":"2025120519351414000_67.5.396.18","doi-asserted-by":"publisher","DOI":"10.1038\/35093050"},{"key":"2025120519351414000_67.5.396.19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206324200"},{"key":"2025120519351414000_67.5.396.20","doi-asserted-by":"publisher","DOI":"10.1210\/er.2002-0012"},{"key":"2025120519351414000_67.5.396.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.004"},{"key":"2025120519351414000_67.5.396.22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.227496"},{"key":"2025120519351414000_67.5.396.23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00526.2002"},{"key":"2025120519351414000_67.5.396.24","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.1946"},{"key":"2025120519351414000_67.5.396.25","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021509"},{"key":"2025120519351414000_67.5.396.26","first-page":"824","article-title":"Ultrastructural findings of biliary epithelial cells and hepatocytes in primary biliary cirrhosis","volume":"12","author":"Naka","year":"1979","journal-title":"J Clin Electron Microscopy"},{"key":"2025120519351414000_67.5.396.27","first-page":"345","article-title":"Electron microscopy of liver lesions in primary biliary cirrhosis","volume":"32","author":"Tobe","year":"1982","journal-title":"Acta Pathol Jpn"},{"key":"2025120519351414000_67.5.396.28","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260604"},{"key":"2025120519351414000_67.5.396.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00105-8"},{"key":"2025120519351414000_67.5.396.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00171-4"},{"key":"2025120519351414000_67.5.396.31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00093.x"},{"key":"2025120519351414000_67.5.396.32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2008.01976.x"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jclinpath-2013-201815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T03:35:26Z","timestamp":1764992126000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2013-201815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,29]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,4,12]]},"published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1136\/jclinpath-2013-201815"],"URL":"https:\/\/doi.org\/10.1136\/jclinpath-2013-201815","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"type":"print","value":"0021-9746"},{"type":"electronic","value":"1472-4146"}],"subject":[],"published":{"date-parts":[[2013,11,29]]}}}