help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sasaki, M.
Right arrow Articles by Nakanuma, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sasaki, M.
Right arrow Articles by Nakanuma, Y.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Bile Duct Diseases
*Cirrhosis
Hazardous Substances DB
*HYDROGEN PEROXIDE
(American Journal of Pathology. 2006;169:831-845.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051237

Decreased Expression of Bmi1 Is Closely Associated with Cellular Senescence in Small Bile Ducts in Primary Biliary Cirrhosis

Motoko Sasaki, Hiroko Ikeda, Yasunori Sato and Yasuni Nakanuma

From the Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

Cellular senescence of biliary epithelial cells with p16INK4a and p21WAF1/Cip expression in damaged small bile ducts may be critical for progressive bile duct loss in primary biliary cirrhosis. We investigated the involvement of bmi1, a polycomb group gene repressing p16INK4a expression, in the pathogenesis of biliary cellular senescence. Bmi1 expression was examined immunohistochemically in livers taken from the patients with primary biliary cirrhosis (n = 18) and other diseased (n = 19) and normal livers (n = 16). We examined the effect of oxidative stress and a short interference RNA (siRNA) targeting bmi1 on cellular senescence in cultured mouse biliary epithelial cells. Bmi1 was widely expressed in the nuclei of biliary epithelial cells in the control livers. In contrast, bmi1 expression was significantly decreased in damaged small bile ducts in 43% of livers with primary biliary cirrhosis of stage 1/2, coordinating with the increased p16INK4a expression. In cultured biliary epithelial cells, oxidative stress by H2O2 treatment significantly decreased bmi1 expression, followed by increased P16INK4a expression. A knockdown of bmi1 induced increased p16INK4a expression, decreased cell proliferation, and increased cellular senescence. In conclusion, the decreased bmi1 expression caused by oxidative stress may be involved in the pathogenesis of cellular senescence of biliary epithelial cells in primary biliary cirrhosis.




This article has been cited by other articles:


Home page
 FASEB J.Home page
T. A. Klimova, E. L. Bell, E. H. Shroff, F. D. Weinberg, C. M. Snyder, G. P. Dimri, P. T. Schumacker, G. R. S. Budinger, and N. S. Chandel
Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS
FASEB J, March 1, 2009; 23(3): 783 - 794.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Sato, K. Harada, S. Ozaki, S. Furubo, K. Kizawa, T. Sanzen, M. Yasoshima, H. Ikeda, M. Sasaki, and Y. Nakanuma
Cholangiocytes with Mesenchymal Features Contribute to Progressive Hepatic Fibrosis of the Polycystic Kidney Rat
Am. J. Pathol., December 1, 2007; 171(6): 1859 - 1871.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
M. Sasaki, H. Ikeda, S. Sawada, Y. Sato, and Y. Nakanuma
Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis
J. Clin. Pathol., October 1, 2007; 60(10): 1102 - 1107.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.