{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:51:19Z","timestamp":1761630679373,"version":"3.44.0"},"reference-count":27,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2014,3,3]]},"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Oestrogen has been speculated to play an important role in the pathogenesis of primary biliary cirrhosis (PBC), which mainly affects middle-aged and old-aged females because biliary epithelial cells (BECs) are known to express oestrogen receptors (ERs). Oestrogen-related receptors (ERRs) are constitutively active without oestrogen and competitively inhibit the ER-dependent effects of oestrogen. We clarified the effects of oestrogen and the significance of ERRs along with their association with the pathogenesis of cholangiopathy in PBC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated the expression of ERs and ERRs and the apoptosis-related cell kinetics in BECs using cultured human BECs and human liver specimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Although cultured human BECs and the interlobular bile ducts in the liver expressed ER\u03b2, in cultured BECs, oestrogen treatment did not induce significant cell proliferation but increased the expression of a negative cell proliferation regulator (14-3-3\u03c3 protein). The cultured BECs constantly expressed ERR\u03b1 and ERR\u03b3, and oestrogen downregulated the ERR\u03b3 expression. Furthermore, the ERR\u03b3 expression was determined in the intrahepatic bile ducts and was stronger in the middle-aged and old-aged females, particularly those with PBC, than in the younger females. The ERR\u03b3 ligand activated a transcription factor, SP1, and enhanced the expression of the pro-apoptotic Bcl-2 family molecules and Bcl-2 inhibitor-induced apoptosis in cultured BECs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Although oestrogen downregulates the ERR\u03b3 expression, the increased ERR\u03b3 expression under oestrogen-deficient conditions increases the susceptibility to Bcl-2 family-mediated apoptosis in cultured human BECs of females, particularly those with PBC. Understanding the oestrogen-mediated cell kinetics is important for elucidating the pathogenesis of cholangiopathy in PBC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2013-201735","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:53:41Z","timestamp":1396313621000},"page":"566-572","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Significance of oestrogen-related receptor \u03b3 on biliary epithelial cells in the pathogenesis of 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, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kakuda","family":"Yuko","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University 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