dc.contributor.author |
Araki, Hiromitsu |
en |
dc.contributor.author |
Tamada, Y |
en |
dc.contributor.author |
Imoto, S |
en |
dc.contributor.author |
Dunmore, B |
en |
dc.contributor.author |
Sanders, D |
en |
dc.contributor.author |
Humphreys, S |
en |
dc.contributor.author |
Nagasahi, M |
en |
dc.contributor.author |
Doi, A |
en |
dc.contributor.author |
Nakanishi, Y |
en |
dc.contributor.author |
Yasuda, K |
en |
dc.contributor.author |
Tomiyasu, Y |
en |
dc.contributor.author |
Tashiro, K |
en |
dc.contributor.author |
Print, Cristin |
en |
dc.contributor.author |
Charnock-Jones, D |
en |
dc.contributor.author |
Kuhara, S |
en |
dc.contributor.author |
Miyano, S |
en |
dc.date.accessioned |
2012-04-02T02:50:10Z |
en |
dc.date.issued |
2009 |
en |
dc.identifier.citation |
ANGIOGENESIS 12(3):221-229 01 Sep 2009 |
en |
dc.identifier.issn |
0969-6970 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/16369 |
en |
dc.description.abstract |
Abstract Fenofibrate is a synthetic ligand for the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha and has been widely used in the treatment of metabolic disorders, especially hyperlipemia, due to its lipid-lowering effect. The molecular mechanism of lipidlowering is relatively well defined: an activated PPARa forms a PPAR–RXR heterodimer and this regulates the transcription of genes involved in energy metabolism by binding to PPAR response elements in their promoter regions, so-called ‘‘trans-activation’’. In addition, fenofi- brate also has anti-inflammatory and anti-athrogenic effects in vascular endothelial and smooth muscle cells. We have limited information about the anti-inflammatory mechanism of fenofibrate; however, ‘‘trans-repression’’ which suppresses production of inflammatory cytokines and adhesion molecules probably contributes to this mechanism. Furthermore, there are reports that fenofibrate affects endothelial cells in a PPARa-independent manner. In order to identify PPARa-dependently and PPARaindependently regulated transcripts, we generated microarray data from human endothelial cells treated with fenofibrate, and with and without siRNA-mediated knockdown of PPARa. We also constructed dynamic Bayesian transcriptome networks to reveal PPARa-dependent and - independent pathways. Our transcriptome network analysis identified growth differentiation factor 15 (GDF15) as a hub gene having PPARa-independently regulated transcripts as its direct downstream children. This result suggests that GDF15 may be PPARa-independent masterregulator of fenofibrate action in human endothelial cells. |
en |
dc.publisher |
Springer Science+Business Media B.V. |
en |
dc.relation.ispartofseries |
Angiogenesis |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
Details obtained from http://www.sherpa.ac.uk/romeo/issn/0969-6970/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Analysis of PPAR±-dependent and PPAR±-independent transcript regulation following fenofibrate treatment of human endothelial cells |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1007/s10456-009-9142-8 |
en |
pubs.begin-page |
221 |
en |
pubs.volume |
12 |
en |
dc.rights.holder |
Copyright: Springer Science+Business Media B.V. |
en |
dc.identifier.pmid |
19357976 |
en |
pubs.end-page |
229 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
96228 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
19357976 |
en |