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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
Volume2
Issue number6
DOIs
Publication statusPublished - 15 Jun 2013

Cite this

Van Rijssel, J., Timmerman, I., Van Alphen, F. P. J., Hoogenboezem, M., Korchynskyi, O., Geerts, D., ... Van Buul, J. D. (2013). The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2. Biology Open, 2(6), 569-579. https://doi.org/10.1242/bio.20134382
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. / The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2. In: Biology Open. 2013 ; Vol. 2, No. 6. pp. 569-579.
@article{61130fe0cd0644328d371c1c54db0efb,
title = "The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2",
abstract = "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.",
author = "{Van Rijssel}, Jos and Ilse Timmerman and {Van Alphen}, {Floris P J} and Mark Hoogenboezem and Olexandr Korchynskyi and Dirk Geerts and Judy Geissler and Reedquist, {Kris A} and Niessen, {Hans W M} and {Van Buul}, {Jaap D}",
year = "2013",
month = "6",
day = "15",
doi = "10.1242/bio.20134382",
language = "English",
volume = "2",
pages = "569--579",
journal = "Biology Open",
issn = "2046-6390",
publisher = "Company of Biologists Ltd",
number = "6",

}

Van Rijssel, J, Timmerman, I, Van Alphen, FPJ, Hoogenboezem, M, Korchynskyi, O, Geerts, D, Geissler, J, Reedquist, KA, Niessen, HWM & Van Buul, JD 2013, 'The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2' Biology Open, vol. 2, no. 6, pp. 569-579. https://doi.org/10.1242/bio.20134382

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

In: Biology Open, Vol. 2, No. 6, 15.06.2013, p. 569-579.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2

AU - Van Rijssel, Jos

AU - Timmerman, Ilse

AU - Van Alphen, Floris P J

AU - Hoogenboezem, Mark

AU - Korchynskyi, Olexandr

AU - Geerts, Dirk

AU - Geissler, Judy

AU - Reedquist, Kris A

AU - Niessen, Hans W M

AU - Van Buul, Jaap D

PY - 2013/6/15

Y1 - 2013/6/15

N2 - 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.

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.

U2 - 10.1242/bio.20134382

DO - 10.1242/bio.20134382

M3 - Article

VL - 2

SP - 569

EP - 579

JO - Biology Open

JF - Biology Open

SN - 2046-6390

IS - 6

ER -

Van Rijssel J, Timmerman I, Van Alphen FPJ, Hoogenboezem M, Korchynskyi O, Geerts D et al. The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2. Biology Open. 2013 Jun 15;2(6):569-579. https://doi.org/10.1242/bio.20134382