Significance of oestrogen-related receptor γ on biliary epithelial cells in the pathogenesis of primary biliary cirrhosis

フォーマット:

論文

責任表示:

Harada, Kenichi ; Kakuda, Yuko ; Sato, Yasunori ; Ikeda, Hiroko ; Nakanuma, Yasuni

言語:

英語

出版情報:

BMJ Publishing Group, 2014-07-01

著者名:

• Harada, Kenichi
• Kakuda, Yuko
• Sato, Yasunori
• Ikeda, Hiroko
• Nakanuma, Yasuni

掲載情報:

Journal of Clinical Pathology

ISSN:

0021-9746      

巻:

67

通号:

7

開始ページ:

566

終了ページ:

572

バージョン:

author

概要:

Aims 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. Methods We investigated the expression of ERs and ERRs and the apoptosis-related cell kinetics in BECs using cultured human BECs and human liver specimens. Results Although cultured human BECs and the interlobular bile ducts in the liver expressed ERβ, in cultured BECs, oestrogen treatment did not induce significant cell proliferation but increased the expression of a negative cell proliferation regulator (14-3-3σ protein). The cultured BECs constantly expressed ERRα and ERβ, and oestrogen downregulated the ERRγ expression. Furthermore, the ERβ 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 ERβ 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. Conclusions Although oestrogen downregulates the ERRγ expression, the increased ERRγ 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. © 2014 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists. 続きを見る

URL:

http://hdl.handle.net/2297/37762