Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats. Academic Article uri icon


  • 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, 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 Ca(2+)/IP3/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte. RESULTS: Cholangiocytes express 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 7-nicotinic receptor stimulated Ca(2+)/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 7-nicotinic receptor signalling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies.

published proceedings

  • Dig Liver Dis

author list (cited authors)

  • Jensen, K., Afroze, S., Ueno, Y., Rahal, K., Frenzel, A., Sterling, M., ... Glaser, S. S.

citation count

  • 22

complete list of 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

publication date

  • January 2013