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dc.date.accessioned2021-01-25T19:57:10Z
dc.date.available2021-01-25T19:57:10Z
dc.date.created2021-01-12T00:40:17Z
dc.date.issued2021
dc.identifier.citationGatti, Francesca Mia, Sobuj Hammarström, Clara Louise Frerker, Nadine Fosby, Bjarte Wang, Junbai Pietka, Wojciech Sundnes, Olav Hol, Johanna Kasprzycka, Monika Haraldsen, Guttorm . Nuclear IL-33 restrains the early conversion of fibroblasts to an extracellular matrix-secreting phenotype. Scientific Reports. 2021, 11:108, 1-13
dc.identifier.urihttp://hdl.handle.net/10852/82599
dc.description.abstractAbstract Interleukin (IL)-33 is a cytokine that appears to mediate fibrosis by signaling via its receptor ST2 (IL-33R/IL1RL1). It is also, however, a protein that after synthesis is sorted to the cell nucleus, where it appears to affect chromatin folding. Here we describe a novel role for nuclear IL-33 in regulating the fibroblast phenotype in murine kidney fibrosis driven by unilateral ureteral obstruction. Transcriptional profiling of IL-33-deficient kidneys 24 h after ligation revealed enhanced expression of fibrogenic genes and enrichment of gene sets involved in extracellular matrix formation and remodeling. These changes relied on intracellular effects of IL-33, because they were not reproduced by treatment with a neutralizing antibody to IL-33 that prevents IL-33R/ST2L receptor signaling nor were they observed in IL-33R/ST2-deficient kidneys. To further explore the intracellular function of IL-33, we established transcription profiles of human fibroblasts, observing that knockdown of IL-33 skewed the transcription profile from an inflammatory towards a myofibroblast phenotype, reflected in higher levels of COL3A1, COL5A1 and transgelin protein, as well as lower expression levels of IL6 , CXCL8 , CLL7 and CCL8 . In conclusion, our findings suggest that nuclear IL-33 in fibroblasts dampens the initial profibrotic response until persistent stimuli, as enforced by UUO, can override this protective mechanism.
dc.languageEN
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleNuclear IL-33 restrains the early conversion of fibroblasts to an extracellular matrix-secreting phenotype
dc.typeJournal article
dc.creator.authorGatti, Francesca
dc.creator.authorMia, Sobuj
dc.creator.authorHammarström, Clara Louise
dc.creator.authorFrerker, Nadine
dc.creator.authorFosby, Bjarte
dc.creator.authorWang, Junbai
dc.creator.authorPietka, Wojciech
dc.creator.authorSundnes, Olav
dc.creator.authorHol, Johanna
dc.creator.authorKasprzycka, Monika
dc.creator.authorHaraldsen, Guttorm
cristin.unitcode185,53,18,71
cristin.unitnameK.G. Jebsen Senter for betennelsesforskning - part UiO
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1869488
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Scientific Reports&rft.volume=11:108&rft.spage=1&rft.date=2021
dc.identifier.jtitleScientific Reports
dc.identifier.volume11
dc.identifier.issue1
dc.identifier.doihttps://doi.org/10.1038/s41598-020-80509-5
dc.identifier.urnURN:NBN:no-85479
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn2045-2322
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/82599/1/Postnr%2B1869488_Gatti_Sci%2BRep_s41598-020-80509-5.pdf
dc.type.versionPublishedVersion
cristin.articleid108
dc.relation.projectHSØ/2008103
dc.relation.projectHSØ/2012081
dc.relation.projectHSØ/2011008
dc.relation.projectEC/FP7/609020
dc.relation.projectHSØ/2013115
dc.relation.projectHSØ/2014032


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