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Journal of Diabetes Research
Volume 2016 (2016), Article ID 7684038, 9 pages
Research Article

Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy

1Centre for Public Health, Queen’s University Belfast, Belfast BT12 6BA, UK
2Conway Institute, University College Dublin, Dublin 4, Ireland

Received 28 November 2014; Revised 18 May 2015; Accepted 24 May 2015

Academic Editor: Georgia Fousteri

Copyright © 2016 Gareth J. McKay et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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. 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 ( 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; ). TFAP2A expression was decreased in an independent dataset (fold change = −1.02; ). 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.