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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.
- 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