Dihydroartemisinin protects blood-brain barrier permeability during sepsis by inhibiting the transcription factor SNAI1.
Fuhong LiuJing LiuHongjie XiangZongguo SunYan LiXiao LiYanjun LiuLiu JuPublished in: Clinical and experimental pharmacology & physiology (2022)
Blood-brain barrier (BBB) injury is involved in the pathogenesis of sepsis-associated encephalopathy. In this study, we used dihydroartemisinin (DHA), a derivative of artemisinin, to treat a cecal ligation and puncture (CLP)-induced mouse sepsis model and a tumour necrosis factor α (TNF-α)-stimulated human cerebral microvessel endothelial cells (hCMEC)/D3 cell line. We found that DHA decreased BBB permeability and increased the expression of the tight junction protein occludin (OCLN) in the CLP model. In hCMEC/D3 cells, DHA decreased TNF-α-induced hyperpermeability and increased the expression of OCLN. DHA also repressed SNAI1 expression in the CLP mouse model and in TNF-α-stimulated hCMEC/D3 cells. These data suggest that DHA protects BBB permeability during sepsis by stimulating the expression of OCLN, by downregulating the expression of the SNAI1 transcription factor.
Keyphrases
- blood brain barrier
- endothelial cells
- poor prognosis
- transcription factor
- high glucose
- cerebral ischemia
- acute kidney injury
- rheumatoid arthritis
- intensive care unit
- mouse model
- fatty acid
- binding protein
- septic shock
- long non coding rna
- diabetic rats
- early onset
- signaling pathway
- oxidative stress
- subarachnoid hemorrhage
- electronic health record
- amino acid
- ultrasound guided
- vascular endothelial growth factor
- protein protein