Spleen tyrosine kinase (Syk) inhibitor fostamatinib limits tissue damage and fibrosis in a bleomycin-induced scleroderma mouse model

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dc.authoridKARACA, Turan/0000-0002-2500-7781
dc.authoridCan, Guray/0000-0002-6054-9244
dc.authorwosidtsokos, george C/O-3360-2013
dc.authorwosidKARACA, Turan/ABD-6669-2020
dc.authorwosidCAN, GÜRAY/AAA-3274-2020
dc.authorwosiddemirtaş, selim/JED-6784-2023
dc.contributor.authorPamuk, O. N.
dc.contributor.authorCan, G.
dc.contributor.authorAyvaz, S.
dc.contributor.authorKaraca, T.
dc.contributor.authorPamuk, G. E.
dc.contributor.authorDemirtas, S.
dc.contributor.authorTsokos, G. C.
dc.date.accessioned2024-06-12T11:13:57Z
dc.date.available2024-06-12T11:13:57Z
dc.date.issued2015
dc.departmentTrakya Üniversitesien_US
dc.description.abstractObjective. The pathogenesis of fibrosis in scleroderma (SSc) is unknown. TGF-beta and platelet-derived growth factor are important in the development of fibrosis and tyrosine kinases are involved in these pathways. The possible antifibrotic effects of various kinase inhibitors in SSc have been studied before. Spleen tyrosine kinase (Syk) is a protein tyrosine kinase which activates intracellular signal transduction pathways; and has been claimed to be involved in the pathogenesis of systemic autoimmune diseases. Inhibition of Syk suppresses IgE-and IgG-associated FcR signal activation in various cell types; and suppresses experimental arthritis and skin and kidney disease in lupus-prone mice. We investigated the ability of a small drug, the Syk inhibitor, fostamatinib, to protect mice from bleomycin-induced SSc. Methods. Four study groups of BALB/c mice were included into this study: control, bleomycin (administered subcutaneously to BALB/c mice for 21 days), bleomycin and fostamatinib (mice fed with chow containing a Syk inhibitor for 21 days), and fostamatinib alone groups. Skin and lung tissue specimens were obtained and evaluated histologically. Results. Treatment with fostamatinib significantly reduced skin thickness and fibrosis. Mice treated with fostamatinib also displayed less fibrosis and inflammation in the lung tissue. Following fostamatinib treatment, Syk, phospho-Syk, and TGF-beta expression decreased in both skin and lung tissues. Conclusion. The Syk inhibitor fostamatinib prevented bleomycin-induced fibrosis and inflammation in the skin and in the lung. The anti-fibrotic effect of fostamatinib is linked to reduced Syk phosphorylation and TGF-beta expression. The Syk pathway appears as a potential molecular target for therapeutic intervention in SSc.en_US
dc.identifier.endpageS22en_US
dc.identifier.issn0392-856X
dc.identifier.issn1593-098X
dc.identifier.issue4en_US
dc.identifier.pmid26148346en_US
dc.identifier.scopus2-s2.0-84946218351en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpageS15en_US
dc.identifier.urihttps://hdl.handle.net/20.500.14551/23748
dc.identifier.volume33en_US
dc.identifier.wosWOS:000362237600002en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherClinical & Exper Rheumatologyen_US
dc.relation.ispartofClinical And Experimental Rheumatologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectSclerodermaen_US
dc.subjectBleomycinen_US
dc.subjectFostamatiniben_US
dc.subjectFibrosisen_US
dc.subjectGrowth-Factor-Betaen_US
dc.subjectSystemic-Sclerosisen_US
dc.subjectImatinib Mesylateen_US
dc.subjectExtracellular-Matrixen_US
dc.subjectDisease Progressionen_US
dc.subjectOpen-Labelen_US
dc.subjectTherapyen_US
dc.subjectSkinen_US
dc.subjectPhaseen_US
dc.subjectCellsen_US
dc.titleSpleen tyrosine kinase (Syk) inhibitor fostamatinib limits tissue damage and fibrosis in a bleomycin-induced scleroderma mouse modelen_US
dc.typeArticleen_US

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