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Journal of Immunology Research
Volume 2014 (2014), Article ID 921285, 8 pages
http://dx.doi.org/10.1155/2014/921285
Research Article

Ursodeoxycholic Acid Influences the Expression of but Not FoxO1 in Patients with Non-Cirrhotic Primary Biliary Cirrhosis

1Medical Biology Laboratory, Pomeranian Medical University, Aleja Powstancow Wlkp. 72, 70-111 Szczecin, Poland
2Angiogenesis Research Group, Faculty of Health, York University, Toronto, Canada
3Division of Transplantation Immunology and Mucosal Biology, Institute of Liver Studies, King’s College London Medical School at King’s College London Hospital, London SE5 9RS, UK
4Liver Unit, University of Birmingham, Birmingham B15 2TH, UK
5Liver Research Laboratories, Pomeranian Medical University, 70-111 Szczecin, Poland
6Department of General, Transplant and Liver Surgery, Liver and Internal Medicine Unit, Warsaw Medical University, 02-092 Warsaw, Poland

Received 3 September 2013; Revised 12 November 2013; Accepted 9 December 2013; Published 5 February 2014

Academic Editor: Eirini I. Rigopoulou

Copyright © 2014 Malgorzata Milkiewicz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Enhanced expression of cell cycle inhibitor suppresses cell proliferation. Ursodeoxycholic acid (UDCA) delays progression of primary biliary cirrhosis (PBC) but its effect on expression is uncertain. Aims. To analyze the expression of and its transcription modulator FoxO1 in patients with PBC, and to assess the impact of UDCA on this pathway. Materials and Methods. The examined human tissue included explanted livers from patients with cirrhotic PBC (), primary sclerosing cholangitis (PSC; ), alcoholic liver disease (ALD; ), and routine liver biopsies from patients with non-cirrhotic PBC (). Healthy liver samples served as controls (). Livers of FoxO-deficient mice were also studied. mRNA and protein expressions were analyzed by real-time PCR and Western blot. Results. expression was increased in cirrhotic and non-cirrhotic PBC. FoxO1 mRNA levels were increased in PBC (8.5-fold increase versus controls). FoxO1 protein expression in PBC was comparable to controls, but it was decreased in patients with PSC and ALD (63% and 70% reduction, respectively; both versus control). UDCA-treated non-cirrhotic patients with PBC showed decreased expression of mRNA. Conclusion. PBC progression is characterized by a FoxO1-independent increase of expression. In early PBC, UDCA may enhance liver regeneration via -dependent mechanism.