Study of regulatory pathway of related molecules in hemolytic uremic syndrome

Eur Rev Med Pharmacol Sci. 2014 Oct;18(19):2886-94.

Abstract

Objective: To screen Hemolytic Uremic Syndrome (HUS) related differentially expressed genes using the microarray data of neonatal microvascular endothelial cells from human skin treated with or without Shiga toxin, and study the the mechanism of HUS from multiple angles.

Materials and methods: The microarray dataset GSE32710 was download from gene expression database GEO (Gene Expression Omnibus), which included a total of 12 samples, 6 samples were treated with Shiga toxin while the others were normal without any treatments. Then the raw chip data were preprocessed by R package, and T-test was utilized for differentially expressed genes screening. The selected differentially expressed genes were subjected to GO functional and KEGG pathway analysis. Following that, human protein interaction network, synergetic effects among the differentially expressed genes and regulation of post-transcriptional miRNA were integrated so as to construct a molecular interaction network associated with HUS and excavate the sub-function modules.

Results: Trough differential expression screening, 195 of HUS related marker genes were obtained, and 294 of gene pairs with significant co-expression were achieved. Molecular interaction network associated with HUS excavated 302 miRNAs and 117 differentially expressed genes, among which miRNA-30c and miRNA-30d may play important roles during the development of HUS.

Conclusions: In this study, we used a method that explained the biological mechanism of HUS systematically from gene transcription level and different levels of biological information such as protein interaction, post-transcriptional regulation of gene expression as well as synergy effects of gene expression, which may provide new therapeutic targets for HUS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / physiology
  • Databases, Genetic*
  • Gene Regulatory Networks / physiology*
  • Hemolytic-Uremic Syndrome / genetics*
  • Hemolytic-Uremic Syndrome / metabolism*
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Protein Interaction Maps / physiology
  • Signal Transduction / physiology*

Substances

  • MicroRNAs