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

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...

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Bibliographic Details
Published in:Biology open 2013-06, Vol.2 (6), p.569-579
Main Authors: Van Rijssel, Jos, Timmerman, Ilse, Van Alphen, Floris P J, Hoogenboezem, Mark, Korchynskyi, Olexandr, Geerts, Dirk, Geissler, Judy, Reedquist, Kris A, Niessen, Hans W M, Van Buul, Jaap D
Format: Article
Language:English
Subjects:
Actin
Arthritis
Cytoskeleton
Endothelium
Ets-2 protein
Extravasation
GEF
Gene regulation
GTPase
Guanine nucleotide-binding protein
Inflammation
Inflammatory diseases
Kinases
Leukocytes
NF-κB protein
Nucleotides
Phosphorylation
Rheumatoid arthritis
Signal transduction
Therapeutic applications
Vascular cell adhesion molecule 1
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Summary: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.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.20134382