Liver, Pancreas and Biliary TractChronic nicotine exposure stimulates biliary growth and fibrosis in normal rats

BackgroundEpidemiological 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.AimsThe aim of this study was to evaluate the effects of chronic administration of nicotine on biliary proliferation and fibrosis in normal rats.MethodsIn 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 Ca2+/IP3/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte.ResultsCholangiocytes 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 Ca2+/ERK1/2-dependent cholangiocyte proliferation.ConclusionChronic 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.