de Launay, D

Frleta, M

Garcia-Perez, S

Garrelfs, M

Gerlag, DM

Reedquist, KA

Tak, PP

van Baarsen, LGM

English

PubMed

M Frleta

LGM van Baarsen

S Garcia-Perez

D de Launay

M Garrelfs

DM Gerlag

PP Tak

KA Reedquist

Springer - Publisher Connector

Differential expression of transcription factors predicted to regulate angiopoietin-1 and -2 genes is associated with specific angiopoietin signatures in RA and PsA synovial tissue

POSTER PRESENTATION Open Access
Differential expression of transcription factors
predicted to regulate angiopoietin-1 and -2
genes is associated with specific angiopoietin
signatures in RA and PsA synovial tissue
M Frleta*, LGM van Baarsen, S Garcia-Perez, D de Launay, M Garrelfs, DM Gerlag, PP Tak, KA Reedquist
From 18th Pediatric Rheumatology European Society (PReS) Congress
Bruges, Belgium. 14-18 September 2011
The angiogenic factors angiopoietin (Ang)-1 and -2 contri-
bute to inflammation and are differentially expressed in
synovial tissue of patients with rheumatoid arthritis (RA)
and psoriatic arthritis (PsA). The underlying mechanisms
for promoting differential expression are unknown. Here,
we identified which cells express Ang-1 and Ang-2 in
synovial tissue, transcription factors (TFs) predicted to
regulate Ang-1 and Ang-2 transcription, and examined
expression of these TFs in RA and PsA synovial tissue.
Immunofluorescent double stainings of RA and PsA
synovial tissue were performed with CD68, CD163, CD3,
CD22 and vWF markers, in combination with antibodies
against Ang-1 and Ang-2, using confocal imaging. In
silico analysis was conducted to identify TF binding sites
in the Ang-1 and Ang-2 promoters, using four different
TF binding site prediction programs. RA synovial expres-
sion of TFs, Ang-1 and Ang-2 was examined in publicly
available gene expression data sets. Candidate TFs were
characterized by real-time PCR (qPCR).
Ang-1 production was detected in CD68 and CD163 –
positive macrophage, CD3-positive T lymphocytes, and
CD22-positive B cells, while Ang-2 expression was
restricted to vWF- positive endothelial cells, as well as
macrophages. In silico studies identified 34 TFs that
were predicted to regulate Ang-1 expression and 22 TFs
which are involved in Ang-2 expression and are upregu-
lated in RA synovial tissue (P< 0.05). Expression of
these TF was readily detected by qPCR in RA and PsA
synovial tissue biopsies.
Our studies suggest that expression of Ang-1 and Ang-2
by different cell types could additional underlie the pre-
viously observed specific Ang-1 high signature in RA,
compared to PsA. Enhanced expression of Ang-1 and
Ang-2 in RA and PsA is strongly associated with expres-
sion of specific TFs, and understanding the mechanisms
leading to the differential expression of these TFs may give
insight into the etiology of RA and PsA.
Published: 14 September 2011
doi:10.1186/1546-0096-9-S1-P278
Cite this article as: Frleta et al.: Differential expression of transcription
factors predicted to regulate angiopoietin-1 and -2 genes is associated
with specific angiopoietin signatures in RA and PsA synovial tissue.
Pediatric Rheumatology 2011 9(Suppl 1):P278.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
* Correspondence: marina@frleta.com
Division of Clinical Immunology and Rheumatology, Academic Medical
Center, University of Amsterdam, Amsterdam, The Netherlands
Frleta et al. Pediatric Rheumatology 2011, 9(Suppl 1):P278
http://www.ped-rheum.com/content/9/S1/P278
© 2011 Frleta et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


Tak PP

Gerlag DM

Garrelfs M

de Launay D

Garcia-Perez S

van Baarsen LGM

Frleta M

Reedquist KA

Directory of Open Access Journals

Pediatric Rheumatology

Crossref

POSTER PRESENTATION Open AccessDifferential expression of transcription factorspredicted to regulate angiopoietin-1 and -2genes is associated with specific angiopoietinsignatures in RA and PsA synovial tissueM Frleta*, LGM van Baarsen, S Garcia-Perez, D de Launay, M Garrelfs, DM Gerlag, PP Tak, KA ReedquistFrom 18th Pediatric Rheumatology European Society (PReS) CongressBruges, Belgium. 14-18 September 2011The angiogenic factors angiopoietin (Ang)-1 and -2 contri-bute to inflammation and are differentially expressed insynovial tissue of patients with rheumatoid arthritis (RA)and psoriatic arthritis (PsA). The underlying mechanismsfor promoting differential expression are unknown. Here,we identified which cells express Ang-1 and Ang-2 insynovial tissue, transcription factors (TFs) predicted toregulate Ang-1 and Ang-2 transcription, and examinedexpression of these TFs in RA and PsA synovial tissue.Immunofluorescent double stainings of RA and PsAsynovial tissue were performed with CD68, CD163, CD3,CD22 and vWF markers, in combination with antibodiesagainst Ang-1 and Ang-2, using confocal imaging. Insilico analysis was conducted to identify TF binding sitesin the Ang-1 and Ang-2 promoters, using four differentTF binding site prediction programs. RA synovial expres-sion of TFs, Ang-1 and Ang-2 was examined in publiclyavailable gene expression data sets. Candidate TFs werecharacterized by real-time PCR (qPCR).Ang-1 production was detected in CD68 and CD163 –positive macrophage, CD3-positive T lymphocytes, andCD22-positive B cells, while Ang-2 expression wasrestricted to vWF- positive endothelial cells, as well asmacrophages. In silico studies identified 34 TFs thatwere predicted to regulate Ang-1 expression and 22 TFswhich are involved in Ang-2 expression and are upregu-lated in RA synovial tissue (P< 0.05). Expression ofthese TF was readily detected by qPCR in RA and PsAsynovial tissue biopsies.Our studies suggest that expression of Ang-1 and Ang-2by different cell types could additional underlie the pre-viously observed specific Ang-1 high signature in RA,compared to PsA. Enhanced expression of Ang-1 andAng-2 in RA and PsA is strongly associated with expres-sion of specific TFs, and understanding the mechanismsleading to the differential expression of these TFs may giveinsight into the etiology of RA and PsA.Published: 14 September 2011doi:10.1186/1546-0096-9-S1-P278Cite this article as: Frleta et al.: Differential expression of transcriptionfactors predicted to regulate angiopoietin-1 and -2 genes is associatedwith specific angiopoietin signatures in RA and PsA synovial tissue.Pediatric Rheumatology 2011 9(Suppl 1):P278.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit* Correspondence: marina@frleta.comDivision of Clinical Immunology and Rheumatology, Academic MedicalCenter, University of Amsterdam, Amsterdam, The NetherlandsFrleta et al. Pediatric Rheumatology 2011, 9(Suppl 1):P278http://www.ped-rheum.com/content/9/S1/P278© 2011 Frleta et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3194644

Differential expression of transcription factors predicted to regulate angiopoietin-1 and -2 genes is associated with specific angiopoietin signatures in RA and PsA synovial tissue

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Springer - Publisher Connector

Directory of Open Access Journals

Crossref