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dc.contributor.authorSchroder, Wayne A
dc.contributor.authorHirata, Thiago D
dc.contributor.authorLe, Thuy T
dc.contributor.authorGardner, Joy
dc.contributor.authorBoyle, Glen M
dc.contributor.authorEllis, Jonathan
dc.contributor.authorNakayama, Eri
dc.contributor.authorPathirana, Dilan
dc.contributor.authorNakaya, Helder I
dc.contributor.authorSuhrbier, Andreas
dc.date.accessioned2020-01-21T05:03:53Z
dc.date.available2020-01-21T05:03:53Z
dc.date.issued2019
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-019-48741-w
dc.identifier.urihttp://hdl.handle.net/10072/390688
dc.description.abstractSerpinB2 (plasminogen activator inhibitor type 2) has been called the “undecided serpin” with no clear consensus on its physiological role, although it is well described as an inhibitor of urokinase plasminogen activator (uPA). In macrophages, pro-inflammatory stimuli usually induce SerpinB2; however, expression is constitutive in Gata6+ large peritoneal macrophages (LPM). Interrogation of expression data from human macrophages treated with a range of stimuli using a new bioinformatics tool, CEMiTool, suggested that SerpinB2 is most tightly co- and counter-regulated with genes associated with cell movement. Using LPM from SerpinB2−/− and SerpinB2R380A (active site mutant) mice, we show that migration on Matrigel was faster than for their wild-type controls. Confocal microscopy illustrated that SerpinB2 and F-actin staining overlapped in focal adhesions and lamellipodia. Genes associated with migration and extracellular matrix interactions were also identified by RNA-Seq analysis of migrating RPM from wild-type and SerpinB2R380A mice. Subsequent gene set enrichment analyses (GSEA) suggested SerpinB2 counter-regulates many Gata6-regulated genes associated with migration. These data argue that the role of SerpinB2 in macrophages is inhibition of uPA-mediated plasmin generation during cell migration. GSEA also suggested that SerpinB2 expression (likely via ensuing modulation of uPA-receptor/integrin signaling) promotes the adoption of a resolution phase signature.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofissue1
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume9
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode1103
dc.subject.keywordsScience & Technology
dc.subject.keywordsMultidisciplinary Sciences
dc.subject.keywordsScience & Technology - Other Topics
dc.subject.keywordsPLASMINOGEN-ACTIVATOR INHIBITOR
dc.subject.keywordsNF-KAPPA-B
dc.titleSerpinB2 inhibits migration and promotes a resolution phase signature in large peritoneal macrophages
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationSchroder, WA; Hirata, TD; Le, TT; Gardner, J; Boyle, GM; Ellis, J; Nakayama, E; Pathirana, D; Nakaya, HI; Suhrbier, A, SerpinB2 inhibits migration and promotes a resolution phase signature in large peritoneal macrophages, Scientific Reports, 2019, 9 (1)
dcterms.dateAccepted2019-08-12
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-01-21T05:00:31Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s). 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorPathirana, Dilan
gro.griffith.authorSchroder, Wayne
gro.griffith.authorBoyle, Glen M.


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