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The Role of Bromodomain and Extraterminal (BET) Proteins in Controlling the Phagocytic Activity of Microglia In Vitro: Relevance to Alzheimer’s Disease

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cris.lastimport.scopus2024-02-12T20:49:51Z
dc.abstract.enThe correct phagocytic activity of microglia is a prerequisite for maintaining homeostasis in the brain. In the analysis of mechanisms regulating microglial phagocytosis, we focused on the bromodomain and extraterminal domain (BET) proteins: Brd2, Brd3, and Brd4, the acetylation code readers that control gene expression in cooperation with transcription factors. We used pharmaco- logical (JQ1) and genetic (siRNA) inhibition of BET proteins in murine microglial cell line BV2. Inhibition of BET proteins reduced the phagocytic activity of BV2, as determined by using a fluores-cent microspheres-based assay and fluorescently labelled amyloid-beta peptides. Gene silencing ex- periments demonstrated that all brain-existing BET isoforms control phagocytosis in microglia. From a set of 84 phagocytosis-related genes, we have found the attenuation of the expression of 14: Siglec1, Sirpb1a, Cd36, Clec7a, Itgam, Tlr3, Fcgr1, Cd14, Marco, Pld1, Fcgr2b, Anxa1, Tnf, Nod1, upon BET inhibition. Further analysis of the mRNA level of other phagocytosis-related genes which were involved in the pathomechanism of Alzheimer’s disease demonstrated that JQ1 significantly re-duced the expression of Cd33, Trem2, and Zyx. Our results indicate the important role of BET pro-teins in controlling microglial phagocytosis; therefore, targeting BET may be the efficient method of modulating microglial activity.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorMatuszewska, Marta
dc.contributor.authorCzapski, Grzegorz
dc.contributor.authorStrawski, Marcin
dc.contributor.authorWilkaniec, Anna
dc.contributor.authorCieślik, Magdalena
dc.date.accessioned2024-01-26T10:46:28Z
dc.date.available2024-01-26T10:46:28Z
dc.date.copyright2022-12-20
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume24
dc.identifier.doi10.3390/IJMS24010013
dc.identifier.issn1422-0067
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/123020
dc.identifier.weblinkhttps://www.mdpi.com/1422-0067/24/1/13/pdf
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.pagesart.no. 13
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enBET
dc.subject.enmicroglia
dc.subject.enBV2
dc.subject.enphagocytosis
dc.subject.enAlzheimer’s disease
dc.titleThe Role of Bromodomain and Extraterminal (BET) Proteins in Controlling the Phagocytic Activity of Microglia In Vitro: Relevance to Alzheimer’s Disease
dc.typeJournalArticle
dspace.entity.typePublication