title: Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats.
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.
  
  
  OBJECTIVE
  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(2+)/IP3/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(2+)/ERK1/2-dependent cholangiocyte proliferation.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Scott & White Healthcare - Digestive Disease Research Center, Temple, TX, USA.
authors.forename: Kendal
authors.initials: K
authors.lastname: Jensen
authors.forename: Syeda
authors.initials: S
authors.lastname: Afroze
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Kinan
authors.initials: K
authors.lastname: Rahal
authors.forename: Amber
authors.initials: A
authors.lastname: Frenzel
authors.forename: Melanie
authors.initials: M
authors.lastname: Sterling
authors.forename: Micheleine
authors.initials: M
authors.lastname: Guerrier
authors.forename: Damir
authors.initials: D
authors.lastname: Nizamutdinov
authors.forename: David E
authors.initials: DE
authors.lastname: Dostal
authors.forename: Fanyin
authors.initials: F
authors.lastname: Meng
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Glaser
mesh_terms: D000199:Actins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000187:drug effects / Q000378:metabolism
chemical_list: D000199:Actins; D003094:Collagen; D005353:Fibronectins; D009538:Nicotine; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D064569:alpha7 Nicotinic Acetylcholine Receptor; C498862:Acta2 protein, rat
keywords: Biliary epithelia; Cholangiocytes; Fibrosis; Nicotinic receptors; Proliferation