TGFbeta and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activation

Hdl Handle:
http://hdl.handle.net/10147/302643
Title:
TGFbeta and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activation
Authors:
Faherty, Noel; O’Donovan, Helen; Kavanagh, David; Madden, Stephen; McKay, Gareth J; Maxwell, Alexander P; Martin, Finian; Godson, Catherine; Crean, John
Citation:
BMC Genomics. 2013 Aug 01;14(1):525
Issue Date:
1-Aug-2013
URI:
http://dx.doi.org/10.1186/1471-2164-14-525; http://hdl.handle.net/10147/302643
Abstract:
Abstract Background CCN2/CTGF is an established effector of TGFβ driven responses in diabetic nephropathy. We have identified an interaction between CCN2 and TGFβ leading to altered phenotypic differentiation and inhibited cellular migration. Here we determine the gene expression profile associated with this phenotype and define a transcriptional basis for differential actin related gene expression and cytoskeletal function. Results From a panel of genes regulated by TGFβ and CCN2, we used co-inertia analysis to identify and then experimentally verify a subset of transcription factors, E2F1 and CREB, that regulate an expression fingerprint implicated in altered actin dynamics and cell hypertrophy. Importantly, actin related genes containing E2F1 and CREB binding sites, stratified by expression profile within the dataset. Further analysis of actin and cytoskeletal related genes from patients with diabetic nephropathy suggests recapitulation of this programme during the development of renal disease. The Rho family member Cdc42 was also found uniquely to be activated in cells treated with TGFβ and CCN2; Cdc42 interacting genes were differentially regulated in diabetic nephropathy. Conclusions TGFβ and CCN2 attenuate CREB and augment E2F1 transcriptional activation with the likely effect of altering actin cytoskeletal and cell growth/hypertrophic gene activity with implications for cell dysfunction in diabetic kidney disease. The cytoskeletal regulator Cdc42 may play a role in this signalling response.
Language:
en
Keywords:
GENETICS

Full metadata record

DC FieldValue Language
dc.contributor.authorFaherty, Noelen_GB
dc.contributor.authorO’Donovan, Helenen_GB
dc.contributor.authorKavanagh, Daviden_GB
dc.contributor.authorMadden, Stephenen_GB
dc.contributor.authorMcKay, Gareth Jen_GB
dc.contributor.authorMaxwell, Alexander Pen_GB
dc.contributor.authorMartin, Finianen_GB
dc.contributor.authorGodson, Catherineen_GB
dc.contributor.authorCrean, Johnen_GB
dc.date.accessioned2013-10-02T10:11:10Z-
dc.date.available2013-10-02T10:11:10Z-
dc.date.issued2013-08-01-
dc.identifier.citationBMC Genomics. 2013 Aug 01;14(1):525en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2164-14-525-
dc.identifier.urihttp://hdl.handle.net/10147/302643-
dc.description.abstractAbstract Background CCN2/CTGF is an established effector of TGFβ driven responses in diabetic nephropathy. We have identified an interaction between CCN2 and TGFβ leading to altered phenotypic differentiation and inhibited cellular migration. Here we determine the gene expression profile associated with this phenotype and define a transcriptional basis for differential actin related gene expression and cytoskeletal function. Results From a panel of genes regulated by TGFβ and CCN2, we used co-inertia analysis to identify and then experimentally verify a subset of transcription factors, E2F1 and CREB, that regulate an expression fingerprint implicated in altered actin dynamics and cell hypertrophy. Importantly, actin related genes containing E2F1 and CREB binding sites, stratified by expression profile within the dataset. Further analysis of actin and cytoskeletal related genes from patients with diabetic nephropathy suggests recapitulation of this programme during the development of renal disease. The Rho family member Cdc42 was also found uniquely to be activated in cells treated with TGFβ and CCN2; Cdc42 interacting genes were differentially regulated in diabetic nephropathy. Conclusions TGFβ and CCN2 attenuate CREB and augment E2F1 transcriptional activation with the likely effect of altering actin cytoskeletal and cell growth/hypertrophic gene activity with implications for cell dysfunction in diabetic kidney disease. The cytoskeletal regulator Cdc42 may play a role in this signalling response.-
dc.language.isoenen
dc.subjectGENETICSen_GB
dc.titleTGFbeta and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activationen_GB
dc.language.rfc3066en-
dc.rights.holderNoel Faherty et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2013-10-01T19:20:28Z-
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