Expression profiles of genes associated with inflammatory responses and oxidative stress in lung after heat stroke

Biosci Rep. 2020 Jun 26;40(6):BSR20192048. doi: 10.1042/BSR20192048.

Abstract

Background: Heat stroke (HS) is a physically dysfunctional illness caused by hyperthermia. Lung, as the important place for gas-exchange and heat-dissipation organ, is often first to be injured. Lung injury caused by HS impairs the ventilation function of lung, which will subsequently cause damage to other tissues and organs. Nevertheless, the specific mechanism of lung injury in heat stroke is still unknown.

Methods: Rat lung tissues from controls or HS models were harvested. The gene expression profile was identified by high-throughput sequencing. DEGs were calculated using R and validated by qRT-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and cell-enrichment were performed using differential expression genes (DEGs). Finally, lung histopathology was accessed by H&E staining.

Results: About 471 genes were identified to be DEGs, of which 257 genes were up-regulated, and 214 genes were down-regulated. The most up-regulated and down-regulated DEGs were validated by qRT-PCR, which confirmed the tendency of expression. GO, KEGG, and protein-protein interaction (PPI)-network analyses disclosed DEGs were significantly enriched in leukocyte migration, response to lipopolysaccharide, NIK/NF-kappaB signaling, response to reactive oxygen species, response to heat, and the hub genes were Tnf, Il1b, Cxcl2, Ccl2, Mmp9, Timp1, Hmox1, Serpine1, Mmp8 and Csf1, most of which were closely related to inflammagenesis and oxidative stress. Finally, cell-enrichment analysis and histopathologic analysis showed Monocytes, Megakaryotyes, and Macrophages were enriched in response to heat stress.

Conclusions: The present study identified key genes, signal pathways and infiltrated-cell types in lung after heat stress, which will deepen our understanding of transcriptional response to heat stress, and might provide new ideas for the treatment of HS.

Keywords: cell enrichment analysis; heat stroke; lung; signal pathway analysis; transcriptome analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Heat Stroke / genetics*
  • Heat Stroke / metabolism
  • Heat Stroke / pathology
  • High-Throughput Nucleotide Sequencing
  • Inflammation Mediators / metabolism
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Oxidative Stress / genetics*
  • Pneumonia / genetics*
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Protein Interaction Maps
  • Rats, Wistar
  • Signal Transduction
  • Transcriptome*

Substances

  • Cytokines
  • Inflammation Mediators