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dc.contributor.author Jiang, D
dc.contributor.author Liang, J
dc.contributor.author Campanella, GS
dc.contributor.author Guo, R
dc.contributor.author Yu, S
dc.contributor.author Xie, T
dc.contributor.author Liu, N
dc.contributor.author Jung, Y
dc.contributor.author Homer, R
dc.contributor.author Meltzer, EB
dc.contributor.author Li, Y
dc.contributor.author Tager, AM
dc.contributor.author Goetinck, PF
dc.contributor.author Luster, AD
dc.contributor.author Noble, PW
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:27:54Z
dc.date.issued 2010-06
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20484822
dc.identifier 38644
dc.identifier.citation J Clin Invest, 2010, 120 (6), pp. 2049 - 2057
dc.identifier.uri http://hdl.handle.net/10161/4322
dc.description.abstract Pulmonary fibrosis is a progressive, dysregulated response to injury culminating in compromised lung function due to excess extracellular matrix production. The heparan sulfate proteoglycan syndecan-4 is important in mediating fibroblast-matrix interactions, but its role in pulmonary fibrosis has not been explored. To investigate this issue, we used intratracheal instillation of bleomycin as a model of acute lung injury and fibrosis. We found that bleomycin treatment increased syndecan-4 expression. Moreover, we observed a marked decrease in neutrophil recruitment and an increase in both myofibroblast recruitment and interstitial fibrosis in bleomycin-treated syndecan-4-null (Sdc4-/-) mice. Subsequently, we identified a direct interaction between CXCL10, an antifibrotic chemokine, and syndecan-4 that inhibited primary lung fibroblast migration during fibrosis; mutation of the heparin-binding domain, but not the CXCR3 domain, of CXCL10 diminished this effect. Similarly, migration of fibroblasts from patients with pulmonary fibrosis was inhibited in the presence of CXCL10 protein defective in CXCR3 binding. Furthermore, administration of recombinant CXCL10 protein inhibited fibrosis in WT mice, but not in Sdc4-/- mice. Collectively, these data suggest that the direct interaction of syndecan-4 and CXCL10 in the lung interstitial compartment serves to inhibit fibroblast recruitment and subsequent fibrosis. Thus, administration of CXCL10 protein defective in CXCR3 binding may represent a novel therapy for pulmonary fibrosis.
dc.format.extent 2049 - 2057
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI38644
dc.subject Animals
dc.subject Bleomycin
dc.subject Extracellular Matrix
dc.subject Fibroblasts
dc.subject Fibrosis
dc.subject Glycosaminoglycans
dc.subject Heparan Sulfate Proteoglycans
dc.subject Lung
dc.subject Lung Diseases, Interstitial
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Knockout
dc.subject Pulmonary Fibrosis
dc.subject Syndecan-4
dc.title Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-6-0 en_US
duke.description.endpage 2057 en_US
duke.description.issue 6 en_US
duke.description.startpage 2049 en_US
duke.description.volume 120 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20484822
pubs.issue 6
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Faculty
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Pulmonary, Allergy, and Critical Care Medicine
pubs.publication-status Published
pubs.volume 120
dc.identifier.eissn 1558-8238

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