期刊
DIGESTIVE AND LIVER DISEASE
卷 45, 期 9, 页码 754-761出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.dld.2013.02.023
关键词
Biliary epithelia; Cholangiocytes; Fibrosis; Nicotinic receptors; Proliferation
资金
- Department of Veteran's Affairs Career Development Award-2
- Scott & White Hospital, Department of Internal Medicine
- Scott and White Research Advancement award
- NIH [DK081442]
- NSF-STEP Grant The Central Texas 2-STEP
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, alpha 7-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 Ca2+/IP3/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte. Results: Cholangiocytes express alpha 7-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 alpha 7-nicotinic receptor stimulated Ca2+/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 alpha 7-nicotinic receptor signalling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
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