Involvement of NEK2 and NEK9 in LPS - induced endothelial barrier dysfunction

Microvasc Res. 2024 Mar:152:104651. doi: 10.1016/j.mvr.2023.104651. Epub 2024 Jan 2.

Abstract

Endothelial hyperpermeability is the hallmark of severe lung injury, including acute respiratory distress syndrome. Despite the fact that Never In Mitosis A (NIMA)-related kinase 2 (NEK2) and NEK9 mediate fundamental cellular processes, our knowledge on their role in barrier function is limited. Herein we show that NEK2 and NEK9 inhibition suppresses LPS-induced paracellular hyperpermeability and myosin light chain 2 activation in endothelial cells. Moreover, the expression levels of both kinases were elevated in inflamed mouse lungs. Based on those findings, we raise the possibility that NEK2 and NEK9 may serve as novel therapeutic targets in lung inflammatory disease.

Keywords: Barrier integrity; Inflammation; Permeability.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Endothelial Cells* / metabolism
  • Endothelium
  • Lipopolysaccharides* / pharmacology
  • Lung / metabolism
  • Mice
  • Signal Transduction

Substances

  • Lipopolysaccharides
  • Nek9 protein, mouse
  • Nek2 protein, mouse