Genes regulated/modulated by jagged1 in endothelial cells during inflammation

Proinflammatory activation of endothelial cells leads to recruitment of leukocytes by upregulation of adhesion molecules and presentation of chemoattractants. In response to such activation there is also a strong shift in the endothelial expression of Notch ligands, with downregulation of Dll4 and a upregulation of JAG1. To assess whether Jagged1 would affect the endothelial activation profile, we suppressed JAG1 expression during IL-1-induced activation by means of siRNA and performed a genome-wide transcriptome analysis. Our results show for the first time that Jagged1 modulates the transcription profile of activated endothelial cells and describe data that imply a role for Jagged1 in sharpening the inflammatory profile of the vasculature, giving it an edge towards leukocyte recruitment. These findings imply that Jagged1 might be a potential therapeutic target to attenuate inflammation and reduce tissue damage in inflammatory diseases.

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Poulsen LC, Edelmann RJ, Krüger S, Diéguez-Hurtado R, Shah A, Stav-Noraas TE, Renzi A, Szymanska M, Wang J, Ehling M, Benedito R, Kasprzycka M, Bækkevold E, Sundnes O, Midwood KS, Scott H, Collas P, Siebel CW, Adams RH, Haraldsen G, Sundlisæter E, Hol J