Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset

Int J Mol Med. 2015 Jul;36(1):103-12. doi: 10.3892/ijmm.2015.2220. Epub 2015 May 22.

Abstract

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, which causes visual disability and blindness. Several studies have used gene expression profiling of DR to identify the key genes involved in this process; however, few studies have focused on the associated pathways and transcription factors (TFs), or on the co-expression patterns at the multiple pathways level. In this study, we employed a microarray dataset from the public database library of the Gene Expression Omnibus (GEO) associated with DR and applied gene set enrichment analysis (GSEA) to this dataset and performed candidate TF selection. As a result, 10 upregulated pathways, including the type I diabetes mellitus and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as 59 downregulated pathways, including the ErbB signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway, were identified as DR‑related pathways. The majority of these pathways have been previously identified, but some were novel. Finally, co-expression networks of related pathways were constructed using the significant core genes and TFs, such as PPARγ and SMAD4. The results of our study may enhance our understanding of the molecular mechanisms associated DR at the genome-wide level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks / genetics*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Signal Transduction / genetics
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors
  • SMAD4 protein, human
  • Smad4 Protein
  • Transcription Factors
  • MTOR protein, human
  • ErbB Receptors
  • TOR Serine-Threonine Kinases