Transcriptomic analyses and experimental verification reveal potential biomarkers and biological pathways of urinary tract infection

Bioengineered. 2021 Dec;12(1):8529-8539. doi: 10.1080/21655979.2021.1987081.

Abstract

Urinary tract infection (UTI) is a common infectious disease. Urinary tract pathogenic Escherichia coli (UPEC) is the main cause of UTIs. At present, antibiotics are mainly used for the treatment of UTIs. However, with the increase of drug resistance, the course of the disease is prolonged. Therefore, identifying the receptors and signal pathways of host cells and tissues will further our understanding of the pathogenesis of UTIs and help in the development of new drug treatments. We used two public microarray datasets (GSE43790, GSE124917) in the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between UTI and normal cell samples. A functional analysis based on Gene Ontology (GO) data, a pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data and a protein-protein interaction analysis identified the main potential biomarkers and verified them in animal tissues. A total of 147 up-regulated genes and 40 down-regulated genes were identified. GO enrichment analysis showed that these functional changes relate to the terms response to lipopolysaccharide, regulation of cytokine production, and regulation of the inflammatory response. KEGG analysis indicated that urinary tract infections likely involve the TNF-αsignaling pathways. The 20 hub genes were selected from the protein-protein interaction network, and the highly significant hub genes were verified by animal experiments. Our findings provide potential targets for exploring new treatments for urinary tract infections. After a comprehensive analysis of the GEO database, these results may facilitate development of new diagnosis and treatment strategies for urinary tract infections.

Keywords: Differentially expressed gene; protein-protein interaction network; tissue-specific gene expression; urinary tract infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Databases, Genetic
  • Down-Regulation / genetics
  • Female
  • Gene Expression Profiling
  • Humans
  • Middle Aged
  • Organ Specificity / genetics
  • Protein Interaction Maps / genetics
  • Signal Transduction / genetics*
  • Transcriptome / genetics*
  • Up-Regulation / genetics
  • Urinary Tract Infections* / genetics
  • Urinary Tract Infections* / metabolism

Substances

  • Biomarkers

Grants and funding

This work was supported by the National Key Research and Development Program of China (2017YFC1703202), the Jilin Scientific and Technological of Chinese Medicine Program (2019023), the Inheritance and Innovation of Chinese Medicine of ‘Millions of Standouts’ Project (the Project of Qihuang), the Inheritance Workroom of the Chinese Medicine Master Wang Lie.Ministry of Science and Technology of the People´s Republic of China [2017YFC1703202];Science and Technology Department of Jilin Province [none];State Administration of Traditional Chinese Medicine of the People’s Republic of China [2019023].