NEK2 inhibition alleviates lipopolysaccharide-induced endothelial injury.

ASPET discovery Pub Date : 2025-01-01 Epub Date: 2025-03-18 DOI:10.1016/j.aspetd.2025.100002
Saikat Fakir, Md Matiur Rahman Sarker, Madan Sigdel, Nektarios Barabutis
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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.

抑制NEK2可减轻脂多糖诱导的内皮损伤。
内皮屏障调节物质在广泛表面的转移,血管渗漏可能导致各种炎症,包括急性呼吸窘迫综合征和败血症。NEK2在调节细胞过程中具有重要作用,其过表达与人类疾病有关。本研究探讨NEK2抑制剂NCL 00017509在内皮屏障功能障碍和炎症中的作用。我们的研究结果表明,上述化合物有效抑制脂多糖诱导的Cofilin和MLC2的激活,这是至关重要的细胞骨架成分。NEK2抑制降低了暴露于脂多糖的细胞内皮细胞旁通透性、活性氧的产生和关键炎症蛋白(如ERK1/2、P38、STAT1和STAT3)的磷酸化。进一步研究NEK2抑制剂在临床前直接和间接肺损伤模型中的应用将证实我们的发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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