title: Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis.
abstract: Intestinal trefoil factor (ITF) promotes epithelial cell migration and mucosal restitution during inflammation. We used real-time quantitative PCR, in situ nucleic acid hybridization, and immunohistochemistry to study the expression of the ITF gene and protein expression in the liver of primary biliary cirrhosis (PBC) and controls. There were significantly higher levels of ITF messenger RNA (mRNA) in PBC liver compared with primary sclerosing cholangitis (PSC) (P <.05) or normal controls (P <.001) and also higher in hepatitis C virus (HCV) liver (P <.05) and cryptogenic cirrhosis (P <.01) compared with normal controls. However, only in PBC was there a significant difference between small (interlobular and bile ductules) and large (intrahepatic and septal) bile ducts. Using in situ hybridization, the highest levels of ITF gene expression were localized to the large bile ducts in PBC. This differential expression of ITF was also noted at the protein level. Thus, in PBC, although 92% of large bile ducts expressed the ITF protein, only 2% of small bile ducts (P <.0001) expressed ITF. In contrast, in control livers, 34% of large bile ducts and 13% of small bile ducts expressed ITF. ITF protein is absent in small bile ducts in all stages of PBC. In conclusion, the expression of ITF may play an important role in bile duct damage. In small bile ducts, ITF production in response to damage is absent, making such cells vulnerable to damage and providing a thesis for the selective loss of small, but not large, bile ducts in PBC.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis 95616, USA.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Patrick S c
authors.initials: PS
authors.lastname: Leung
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kenny
authors.forename: Judy
authors.initials: J
authors.lastname: Van De Water
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishioka
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Giraud
authors.forename: James
authors.initials: J
authors.lastname: Neuberger
authors.forename: Gordon
authors.initials: G
authors.lastname: Benson
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kaul
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D001659:Biliary Tract / Q000473:pathology*; D001706:Biopsy; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008105:Liver Cirrhosis, Biliary / Q000473:pathology / Q000503:physiopathology*; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
chemical_list: D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3