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dc.contributor.authorSchuliga, M
dc.contributor.authorJaffar, J
dc.contributor.authorHarris, T
dc.contributor.authorKnight, DA
dc.contributor.authorWestall, G
dc.contributor.authorStewart, AG
dc.date.accessioned2020-12-22T04:34:24Z
dc.date.available2020-12-22T04:34:24Z
dc.date.issued2017-01-31
dc.identifierpii: srep41770
dc.identifier.citationSchuliga, M., Jaffar, J., Harris, T., Knight, D. A., Westall, G. & Stewart, A. G. (2017). The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/srep41770.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/258093
dc.description.abstractThe role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5-15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5-6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung fibrosis.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF
dc.typeJournal Article
dc.identifier.doi10.1038/srep41770
melbourne.affiliation.departmentPharmacology and Therapeutics
melbourne.affiliation.departmentUniversity General
melbourne.source.titleScientific Reports
melbourne.source.volume7
melbourne.source.issue1
melbourne.identifier.nhmrc1022048
melbourne.identifier.nhmrc1059665
melbourne.identifier.nhmrc1023185
dc.rights.licenseCC BY
melbourne.elementsid1184054
melbourne.contributor.authorStewart, Alastair
melbourne.contributor.authorSchuliga, Michael
melbourne.contributor.authorHarris, Trudi
dc.identifier.eissn2045-2322
melbourne.identifier.fundernameidNHMRC, 1022048
melbourne.identifier.fundernameidNHMRC, 1059665
melbourne.identifier.fundernameidNHMRC, 1023185
melbourne.accessrightsOpen Access


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