The potential involvement of JAK-STAT signaling pathway in the COVID-19 infection assisted by ACE2

Gene. 2021 Feb 5:768:145325. doi: 10.1016/j.gene.2020.145325. Epub 2020 Nov 28.

Abstract

COVID-19, a novel identified coronavirus disease due to Severe Acute Respiratory Syndrome coronaviruses 2 (SARS-Cov-2) infection, has posed a significant threat to public health worldwide. It has been reported COVID-19 keeps substantial nucleotide similarity and shares common receptor, Angiotensin-converting enzyme 2 (ACE2) with Severe Acute Respiratory Syndrome coronaviruses (SARS-Cov). Here, we investigated the gene expression of ACE2 and identified associated pathways of SARS-Cov as a useful reference for a deepening understanding of COVID-19. The results indicated the ACE2 was overexpressed in human airway epithelial cells (HAEs), especially at 72 h after SARS-Cov infection. We found ACE2 might regulate immune response through immunological activation-associated pathways in the process of in both SARS-Cov and SARS-Cov-2 infection, where the activation of B cells, macrophages, helper T cells 1 (Th1 cells) and the inhibition of Foxp3 + regulatory T (Treg) cells and CD8 + T cells were found to be prominent. Finally, significant correlation between ACE2 and JAK-STAT signaling pathway was identified which indicate that JAK-STAT signaling pathway might involve in the downstream action of the overactivation of ACE2. These findings are expected to gain a further insight into the action mechanism of COVID-19 infection and provide a promising target for designing effective therapeutic strategies.

Keywords: ACE2; COVID-19; Immune cell; JAK-STAT signaling pathway; Signal-gene GSEA.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism*
  • COVID-19 / genetics
  • COVID-19 / metabolism*
  • Case-Control Studies
  • Humans
  • Janus Kinases / metabolism*
  • Lung / immunology
  • Lung / virology
  • STAT Transcription Factors / metabolism*
  • Signal Transduction
  • Transcriptome

Substances

  • STAT Transcription Factors
  • Janus Kinases
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2