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Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni. Pereira, Thiago A Syn, Wing-Kin Machado, Mariana V Vidigal, Paula V Resende, Vivian Voieta, Izabela Xie, Guanhua Otoni, Alba Souza, Márcia M Santos, Elisângela T Chan, Isaac S Trindade, Guilherme VM Choi, Steve S Witek, Rafal P Pereira, Fausto E Secor, William E Andrade, Zilton A Lambertucci, José Roberto Diehl, Anna Mae
dc.coverage.spatial England 2015-12-04T02:49:52Z 2015-11
dc.identifier CS20150117
dc.description.abstract Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity.
dc.language eng
dc.publisher Portland Press Ltd.
dc.relation.ispartof Clin Sci (Lond)
dc.relation.isversionof 10.1042/CS20150117
dc.subject Schistosomiasis mansoni
dc.subject Symmers' fibrosis
dc.subject cholangiocyte
dc.subject ductular proliferation
dc.subject osteopontin
dc.subject portal hypertension
dc.subject Adolescent
dc.subject Adult
dc.subject Animals
dc.subject Antigens, Helminth
dc.subject Bile Ducts
dc.subject Cell Line
dc.subject Cell Proliferation
dc.subject Cells, Cultured
dc.subject Female
dc.subject Hepatic Stellate Cells
dc.subject Host-Parasite Interactions
dc.subject Humans
dc.subject Hypertension, Portal
dc.subject Immunohistochemistry
dc.subject Kupffer Cells
dc.subject Liver Cirrhosis
dc.subject Male
dc.subject Mice
dc.subject Middle Aged
dc.subject Osteopontin
dc.subject Rats
dc.subject Reverse Transcriptase Polymerase Chain Reaction
dc.subject Schistosoma
dc.subject Schistosomiasis mansoni
dc.subject Young Adult
dc.title Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.
dc.type Journal article Choi, Steve S|0278358 Diehl, Anna Mae|0314922
pubs.begin-page 875
pubs.end-page 883
pubs.issue 10
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Gastroenterology
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 129
dc.identifier.eissn 1470-8736
duke.contributor.orcid Choi, Steve S|0000-0001-9228-4060

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