Overexpression of mitogen-activated protein kinase phosphatase-1 in endothelial cells reduces blood-brain barrier injury in a mouse model of ischemic stroke

In this study, we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke. We found that overexpression of MKP-1 in ECs reduced infarct volume, reduced the level of inflammatory factors interleukin-1β, interleukin-6, and chemokine C-C motif ligand-2, inhibited vascular injury, and promoted the recovery of sensorimotor and memory/cognitive function. Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase (ERK) 1/2 and the downregulation of occludin expression. Finally, to investigate the mechanism by which MKP-1 exerted these functions in ECs, we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose, and pharmacologically inhibited the activity of MKP-1 and ERK1/2. Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death, cell monolayer leakage, and downregulation of occludin expression, and that inhibiting ERK1/2 can reverse these effects. In addition, co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2. These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2, thereby protecting the integrity of BBB, alleviating brain injury, and im...
Source: Cell Research - Category: Cytology Authors: Source Type: research