RT Journal Article
SR Electronic
T1 The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2
JF Biology Open
JO Biology Open
FD Company of Biologists
SP 569
OP 579
DO 10.1242/bio.20134382
VO 2
IS 6
A1 Van Rijssel, Jos
A1 Timmerman, Ilse
A1 Van Alphen, Floris P. J.
A1 Hoogenboezem, Mark
A1 Korchynskyi, Olexandr
A1 Geerts, Dirk
A1 Geissler, Judy
A1 Reedquist, Kris A.
A1 Niessen, Hans W. M.
A1 Van Buul, Jaap D.
YR 2013
UL http://bio.biologists.org/content/2/6/569.abstract
AB 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.