title: Connective tissue growth factor expression is increased in biliary epithelial cells in biliary atresia.
abstract: OBJECTIVE
  Connective tissue growth factor (CTGF) has been implicated in the pathogenesis of hepatic fibrosis and is elevated in the serum of children with biliary atresia (BA). The objective of this study was to evaluate hepatic CTGF messenger RNA (mRNA) expression and its relationship to hepatic histology in children with BA.
  
  
  METHODS
  Connective tissue growth factor mRNA expression was evaluated by in situ hybridization in 26 liver biopsies from 11 patients with BA, 11 with other diseases, and 4 autopsy controls. Serial sections were immunostained with cell-specific markers to characterize the cells expressing CTGF. Biopsies were scored for CTGF expression (0-4) and inflammation and fibrosis (1-4).
  
  
  RESULTS
  High levels of CTGF expression were observed in 9 of 11 BA with localization to biliary epithelial cells and vascular endothelial cells. Connective tissue growth factor mRNA expression was correlated with fibrosis in BA and all livers. In the 11 patients with other liver diseases, 7 had CTGF expression limited to hepatic stellate cells and vascular endothelial cells. None of the 4 livers in children without liver disease had significant levels of CTGF.
  
  
  CONCLUSIONS
  In BA livers, novel biliary epithelia CTGF mRNA expression is high and correlates with severity of fibrosis. These data support a role for biliary epithelial cell signaling in fibrogenesis.
authors.affiliation: Department of Pediatrics, The Pediatric Liver Center, The Children's Hospital, University of Colorado School of Medicine, Denver, CO 80218, USA. narkewicz.michael@tchden.org
authors.forename: Michael R
authors.initials: MR
authors.lastname: Narkewicz
authors.forename: Arvind
authors.initials: A
authors.lastname: Kasaragod
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.forename: Sean
authors.initials: S
authors.lastname: Pflummer
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Stenmark
mesh_terms: D000293:Adolescent; D000328:Adult; D001344:Autopsy; D001656:Biliary Atresia / Q000235:genetics* / Q000503:physiopathology*; D001659:Biliary Tract / Q000166:cytology; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor