Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy
Joint Authors
McKay, Gareth
Kavanagh, David H.
Crean, John K.
Maxwell, Alexander P.
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-11-30
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Objective.
WNT/β-catenin pathway members have been implicated in interstitial fibrosis and glomerular sclerosis disease processes characteristic of diabetic nephropathy (DN), processes partly controlled by transcription factors (TFs) that bind to gene promoter regions attenuating regulation.
We sought to identify predicted cis-acting transcription factor binding sites (TFBSs) overrepresented within WNT pathway members.
Methods.
We assessed 62 TFBS motif frequencies from the JASPAR databases in 65 WNT pathway genes.
P values were estimated on the hypergeometric distribution for each TF.
Gene expression profiles of enriched motifs were examined in DN-related datasets to assess clinical significance.
Results.
Transcription factor AP-2 alpha (TFAP2A), myeloid zinc finger 1 (MZF1), and specificity protein 1 (SP1) were significantly enriched within WNT pathway genes ( P values < 6.83 × 10−29, 1.34 × 10−11, and 3.01 × 10−6, resp.).
MZF1 expression was significantly increased in DN in a whole kidney dataset (fold change = 1.16; 16% increase; P = 0.03 ).
TFAP2A expression was decreased in an independent dataset (fold change = −1.02; P = 0.03 ).
No differential expression of SP1 was detected.
Conclusions.
Three TFBS profiles are significantly enriched within WNT pathway genes highlighting the potential of in silico analyses for identification of pathway regulators.
Modification of TF binding may possibly limit DN progression, offering potential therapeutic benefit.
American Psychological Association (APA)
McKay, Gareth& Kavanagh, David H.& Crean, John K.& Maxwell, Alexander P.. 2015. Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy. Journal of Diabetes Research،Vol. 2016, no. 2016, pp.1-9.
https://search.emarefa.net/detail/BIM-1108250
Modern Language Association (MLA)
McKay, Gareth…[et al.]. Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy. Journal of Diabetes Research No. 2016 (2016), pp.1-9.
https://search.emarefa.net/detail/BIM-1108250
American Medical Association (AMA)
McKay, Gareth& Kavanagh, David H.& Crean, John K.& Maxwell, Alexander P.. Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy. Journal of Diabetes Research. 2015. Vol. 2016, no. 2016, pp.1-9.
https://search.emarefa.net/detail/BIM-1108250
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1108250