Dexmedetomidine preconditioning ameliorates lung injury induced by pulmonary ischemia/reperfusion by upregulating promoter histone H3K4me3 modification of KGF-2

  • Exp Cell Res. 2021 Sep 15;406(2):112762. doi: 10.1016/j.yexcr.2021.112762.
Huisuo Hong  1 ,  Qingqing Huang  2 ,  Yaoyao Cai  1 ,  Tingting Lin  1 ,  Fangfang Xia  1 ,  Zhousheng Jin  3
Affiliations
  • 1. Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, PR China.
  • 2. Department of Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, PR China. Electronic address: [email protected].
  • 3. Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, PR China. Electronic address: [email protected].
PMID: 34352276 DOI: 10.1016/j.yexcr.2021.112762
Abstract

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.

Keywords
Dexmedetomidine; Endothelial barrier dysfunction; Ischemia/reperfusion; JMJD3; KGF-2; Lung injury.
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