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Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats.

Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats.

Authors :
Jensen, Kendal
Afroze, Syeda
Ueno, Yoshiyuki
Rahal, Kinan
Frenzel, Amber
Sterling, Melanie
Guerrier, Micheleine
Nizamutdinov, Damir
Dostal, David E.
Meng, Fanyin
Glaser, Shannon S.
Source :
Digestive & Liver Disease; Sep2013, Vol. 45 Issue 9, p754-761, 8p
Publication Year :
2013

Abstract

Abstract: Background: Epidemiological studies have indicated smoking to be a risk factor for the progression of liver diseases. Nicotine is the chief addictive substance in cigarette smoke and has powerful biological properties throughout the body. Nicotine has been implicated in a number of disease processes, including increased cell proliferation and fibrosis in several organ systems. Aims: The aim of this study was to evaluate the effects of chronic administration of nicotine on biliary proliferation and fibrosis in normal rats. Methods: In vivo, rats were treated with nicotine by osmotic minipumps for two weeks. Proliferation, α7-nicotinic receptor and profibrotic expression were evaluated in liver tissue, cholangiocytes and a polarized cholangiocyte cell line (normal rat intrahepatic cholangiocyte). Nicotine-dependent activation of the Ca<superscript>2+</superscript>/IP<subscript>3</subscript>/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte. Results: Cholangiocytes express α7-nicotinic receptor. Chronic administration of nicotine to normal rats stimulated biliary proliferation and profibrotic gene and protein expression such as alpha-smooth muscle actin and fibronectin 1. Activation of α7-nicotinic receptor stimulated Ca<superscript>2+</superscript>/ERK1/2-dependent cholangiocyte proliferation. Conclusion: Chronic exposure to nicotine contributes to biliary fibrosis by activation of cholangiocyte proliferation and expression of profibrotic genes. Modulation of α7-nicotinic receptor signalling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
15908658
Volume :
45
Issue :
9
Database :
Supplemental Index
Journal :
Digestive & Liver Disease
Publication Type :
Academic Journal
Accession number :
89705395
Full Text :
https://doi.org/10.1016/j.dld.2013.02.023