title: Expression of osteopontin correlates with portal biliary proliferation and fibrosis in biliary atresia.
abstract: The acquired or perinatal form of biliary atresia is a Th1 fibro-inflammatory disease affecting both the extrahepatic and intrahepatic bile ducts. Osteopontin (OPN) is a Th1 cytokine implicated in several fibro-inflammatory and autoimmune diseases. We examined the expression of OPN in acquired biliary atresia in comparison to normal liver and several pediatric cholestatic liver diseases. We also assessed OPN expression by cultured human bile duct epithelial cells. We found that liver OPN mRNA and protein expression were significantly increased in biliary atresia versus normal and other cholestatic diseases. OPN expression in biliary atresia was localized to epithelium of proliferating biliary structures (ductules and/or ducts) and bile plugs contained therein. No portal biliary OPN expression could be demonstrated in normal liver, syndromic biliary atresia, biliary obstruction not due to biliary atresia, and idiopathic neonatal hepatitis. OPN expression by human bile duct epithelial cells in culture was responsive to IL-2 and TNF-alpha. Our results demonstrate an up-regulation of OPN expression by interlobular biliary epithelium in biliary atresia, which correlates with biliary proliferation and portal fibrosis. These findings suggest a role for OPN in the pathogenesis of biliary atresia.
authors.affiliation: Department of Pediatrics, Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA. p-whitington@northwestern.edu
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.forename: Padmini
authors.initials: P
authors.lastname: Malladi
authors.forename: Hector
authors.initials: H
authors.lastname: Melin-Aldana
authors.forename: Ruba
authors.initials: R
authors.lastname: Azzam
authors.forename: Cara L
authors.initials: CL
authors.lastname: Mack
authors.forename: Atul
authors.initials: A
authors.lastname: Sahai
mesh_terms: D001483:Base Sequence; D001652:Bile Ducts / Q000378:metabolism* / Q000473:pathology*; D001656:Biliary Atresia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002779:Cholestasis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology; D053495:Osteopontin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018076:DNA, Complementary; D007376:Interleukin-2; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin