Selectin E upregulation upon forkhead box P1 loss augments neutrophil infiltration and brain damage in hypertensive intracerebral hemorrhage.

Abstract

Hypertension in the brain may lead to hypertensive intracerebral hemorrhage (HICH), a devastating disease. This study, grounded on bioinformatics insights, aims to investigate the functions of Selectin E (SELE) and forkhead box P1 (FOXP1) in the progression of HICH. Increased SELE expression was detected in the striatum of a mouse model of HICH generated via angiotensin II and L-NAME treatments. Knockdown of SELE alleviated hemorrhage, neutrophil infiltration, and blood-brain barrier (BBB) rupture in the mouse brain. FOXP1, poorly expressed in the HICH mice, was found to repress SELE transcription by binding to its promoter region. Overexpression of FOXP1 resulted in analogous alleviating effects in the HICH mice; however, the effects were abrogated by the additional SELE overexpression. In vitro, human brain microvascular endothelial cells (HBMECs) were treated with thrombin to generate a cellular model of ICH, followed by co-culture with HL-60 cell-derived neutrophils. The FOXP1 overexpression reduced the adhesion of neutrophils, and it alleviated HBMEC apoptosis and permeability while enhancing angiogenesis. Still, these effects were counteracted by the SELE upregulation. In conclusion, this study demonstrates that SELE upregulation upon FOXP1 loss is associated with neutrophil infiltration and BBB rupture in HICH.