Keratinocyte growth factor (KGF)-2 has been highlighted to play a significant role in maintaining the endothelial barrier integrity in lung injury induced by ischemia-reperfusion (I/R). However, the underlying mechanism remains largely unknown. The aims of this study were to determine whether dexmedetomidine preconditioning (DexP) modulates pulmonary I/R-induced lung injury through the alteration in KGF-2 expression. In our I/R-modeled mice, DexP significantly inhibited pathological injury, inflammatory response, and inflammatory cell infiltration, while promoted endothelial barrier integrity and KGF-2 promoter activity in lung tissues. Bioinformatics prediction and ChIP-seq revealed that I/R significantly diminished the level of H3K4me3 modification in the KGF-2 promoter, which was significantly reversed by DexP. Moreover, DexP inhibited the expression of histone demethylase JMJD3, which in turn promoted the expression of KGF-2. In addition, overexpression of JMJD3 weakened the protective effect of DexP on lung injury in mice with I/R. Collectively, the present results demonstrated that DexP ameliorates endothelial barrier dysfunction via the JMJD3/KGF-2 axis.

角质形成细胞生长因子 (KGF)-2 已被强调在维持缺血再灌注 (I/R) 诱导的肺损伤中的内皮屏障完整性方面发挥重要作用。然而，潜在的机制在很大程度上仍然未知。本研究的目的是确定右美托咪定预处理 (DexP) 是否通过改变 KGF-2 表达来调节肺 I/R 诱导的肺损伤。在我们的 I/R 模型小鼠中，DexP 显着抑制病理损伤、炎症反应和炎症细胞浸润，同时促进肺组织中的内皮屏障完整性和 KGF-2 启动子活性。生物信息学预测和 ChIP-seq 显示 I/R 显着降低了 KGF-2 启动子中 H3K4me3 修饰的水平，而 DexP 显着逆转了这一点。而且，DexP 抑制组蛋白去甲基化酶 JMJD3 的表达，进而促进 KGF-2 的表达。此外，JMJD3的过表达减弱了DexP对I/R小鼠肺损伤的保护作用。总的来说，目前的结果表明，DexP 通过 JMJD3/KGF-2 轴改善内皮屏障功能障碍。