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<p>Disruption of the blood-brain barrier (BBB) is an essential pathological outcome of ischemic stroke (IS). This study aimed to prove that Gata1 upregulates Hras and promotes ERK signaling, leading to BBB damage in IS. Middle cerebral artery occlusion (MCAO) was used for in vivo modeling, and cerebrovascular endothelial cell-specific adeno-associated viruses were used for Gata1/Hras expression manipulation. TTC staining, Evans blue extravasation assay, and Western blot analysis were conducted to investigate the role of Gata1 and Hras in BBB injury. Mouse bEnd.3 cells were exposed to oxygen-glucose deprivation (OGD), and lentivirus-mediated genetic interventions were performed. Viability, lactate dehydrogenase release, and BBB permeability were assessed in bEnd.3 cells. The regulation of Gata1 on Hras was examined using ChIP-qPCR and a dual-luciferase assay. Gata1 was upregulated in mice after MCAO, and Gata1 knockdown reduced cerebral infarction and decreased BBB leakage in mice. Gata1 knockdown also alleviated OGD-induced BBB permeability and bEnd.3 cell injury. Gata1 transcriptionally activated Hras and promoted the ERK signaling. Hras reactivation reversed BBB injury in MCAO mice and BBB permeability and bEnd.3 cell injury alleviated by Gata1 knockdown. Overall, Gata1 transcriptionally upregulates Hras expression and activates the ERK signaling to exacerbate BBB dysfunction in mice after MCAO.</p>

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Gata1-mediated Hras transcription stimulates blood-brain barrier injury in ischemic stroke through activation of the ERK pathway

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Kelong Chen,
  • Ling Chen,
  • Huijing Sun,
  • Bin Li

摘要

Disruption of the blood-brain barrier (BBB) is an essential pathological outcome of ischemic stroke (IS). This study aimed to prove that Gata1 upregulates Hras and promotes ERK signaling, leading to BBB damage in IS. Middle cerebral artery occlusion (MCAO) was used for in vivo modeling, and cerebrovascular endothelial cell-specific adeno-associated viruses were used for Gata1/Hras expression manipulation. TTC staining, Evans blue extravasation assay, and Western blot analysis were conducted to investigate the role of Gata1 and Hras in BBB injury. Mouse bEnd.3 cells were exposed to oxygen-glucose deprivation (OGD), and lentivirus-mediated genetic interventions were performed. Viability, lactate dehydrogenase release, and BBB permeability were assessed in bEnd.3 cells. The regulation of Gata1 on Hras was examined using ChIP-qPCR and a dual-luciferase assay. Gata1 was upregulated in mice after MCAO, and Gata1 knockdown reduced cerebral infarction and decreased BBB leakage in mice. Gata1 knockdown also alleviated OGD-induced BBB permeability and bEnd.3 cell injury. Gata1 transcriptionally activated Hras and promoted the ERK signaling. Hras reactivation reversed BBB injury in MCAO mice and BBB permeability and bEnd.3 cell injury alleviated by Gata1 knockdown. Overall, Gata1 transcriptionally upregulates Hras expression and activates the ERK signaling to exacerbate BBB dysfunction in mice after MCAO.