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. 2025:1:100002.
doi: 10.1016/j.aspetd.2025.100002. Epub 2025 Mar 18.

NEK2 inhibition alleviates lipopolysaccharide-induced endothelial injury

Saikat Fakir  1 , Md Matiur Rahman Sarker  1 , Madan Sigdel  1 , Nektarios Barabutis  1
Affiliations

NEK2 inhibition alleviates lipopolysaccharide-induced endothelial injury

Saikat Fakir et al. ASPET Discov. 2025.

Abstract

The endothelial barrier regulates substance transfer across an extensive surface area, and vascular leakage may contribute to various inflammatory conditions, including acute respiratory distress syndrome and sepsis. NEK2 possesses a significant role in regulating cellular processes, and its overexpression has been linked to human disease. The present study investigates the effects of NEK2 inhibitor NCL 00017509 in endothelial barrier dysfunction and inflammation. Our results indicate that the aforementioned compound effectively suppresses lipopolysaccharide-induced activation of Cofilin and MLC2, which are crucial cytoskeletal components. NEK2 inhibition reduced endothelial paracellular permeability, reactive oxygen species generation, and phosphorylation of key inflammatory proteins (eg, ERK1/2, P38, STAT1, and STAT3) in cells exposed to lipopolysaccharide. Further investigation into the application of NEK2 inhibitors in preclinical models of direct and indirect lung injury will substantiate our findings.

Keywords: Endothelial permeability; Lung; Sepsis.

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Conflict of interest statement

Conflict of interest The authors declare no conflict of interests.

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