The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2

Jos Van Rijssel, Ilse Timmerman, Floris P J Van Alphen, Mark Hoogenboezem, Olexandr Korchynskyi, Dirk Geerts, Judy Geissler, Kris A Reedquist, Hans W M Niessen, Jaap D Van Buul

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Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central to this event is increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in gene regulation. However, in inflammation, it is not clear how this is regulated. Here, we show that the guanine-nucleotide exchange factor Trio expression is increased upon inflammatory stimuli in endothelium. Additionally, increased Trio expression was found in the vessel wall of rheumatoid arthritis patients. Trio silencing impaired VCAM-1 expression. Finally, we excluded that Trio-controlled VCAM-1 expression used the classical NFκB or MAP-kinase pathways, but rather acts on the transcriptional level by increasing phosphorylation and nuclear translocalization of Ets2. These data implicate Trio in regulating inflammation and provide novel targets for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis.

Original languageEnglish
Pages (from-to)569-579
Number of pages11
JournalBiology Open
Issue number6
Publication statusPublished - 15 Jun 2013

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