The Potential Role of Protein Tyrosine Phosphatase, Receptor Type C (CD45) in the Intestinal Ischemia-Reperfusion Injury

J Comput Biol. 2020 Aug;27(8):1303-1312. doi: 10.1089/cmb.2019.0244. Epub 2019 Dec 20.

Abstract

This study was designed to identify several key genes and their functions in preventing or ameliorating intestinal ischemia-reperfusion (IR) injury, which could provide rationale for further exploring the regulatory mechanisms or clinical treatment for intestinal IR injury. The microarray GSE37013 of human intestinal IR injury was downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) with changes of reperfusion time were screened using Short Time-series Expression Miner, followed by function enrichment analysis, protein-protein interaction (PPI) network, and module construction. Subsequently, the key DEGs were identified with VEEN analysis based on the significant results of function enrichment analysis and PPI module. Finally, the gene-drug interactions were predicted using DGIdb 2.0. The DEGs of intestinal IR injury were significantly divided into three clusters with changes of reperfusion time. The genes in the three clusters were mainly enriched in transmembrane transport, defense responses, and cellular component assembly related pathways, respectively. There were 121 nodes and 281 interactions in PPI network, including one significant submodule. Protein tyrosine phosphatase, receptor type C (PTPRC) was a hub code both in PPI network and in submodule. A total of eight key DEGs were identified but only PTPRC was predicted to be interacted with eight drugs, such as infliximab. Totally, eight key genes associated with intestinal IR were identified; PTPRC especially was the most prominent potential drug target. These findings provided several potential therapeutic targets or potential breakthrough area in the study of intestinal IR injury.

Keywords: differentially expressed genes; function analysis; gene–drug interactions; intestinal ischemia–reperfusion injury; time series analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Computational Biology*
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks / genetics
  • Humans
  • Intestines / injuries*
  • Intestines / pathology
  • Leukocyte Common Antigens / genetics*
  • MicroRNAs / genetics
  • Microarray Analysis
  • Protein Interaction Maps / genetics
  • Protein Tyrosine Phosphatases / genetics
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology

Substances

  • Carrier Proteins
  • MicroRNAs
  • Leukocyte Common Antigens
  • PTPRC protein, human
  • Protein Tyrosine Phosphatases