Abstract
Discoidin domain receptor 1 (DDR1) has been shown to mediate matrix metalloproteinase-9 (MMP-9) secretions and degrade all extracellular matrix compounds in mammalian tumor cells. We hypothesized that DDR1 expression will be elevated and the blood–brain barrier (BBB) will be damaged after focal cerebral ischemia in rats. Inhibiting DDR1 expression can alleviate BBB disruption and cerebral ischemic damage via down-regulation of MMP-9 expression and activity. To test our hypothesis, we injected specific DDR1 siRNA into ipsilateral ischemic lateral ventricles in a focal ischemic model. Our results showed that phospho-DDR1 expression increased after ischemia/reperfusion (I/R) injury (p<0.01). Inactivation of DDR1 by specific siRNA caused a decrease in phospho-DDR1 and MMP-9 expression in the ischemic cortex, reduced stroke-induced infarct volume, and alleviated BBB disruption in rat brain following I/R injury (p<0.01). Our results suggested that DDR1-siRNA attenuates phospho-DDR1 and MMP-9 upregulation, which was followed by a reduction in infarction and BBB disruption in the ischemic brain after I/R injury. DDR1 may represent a molecular target for the prevention of BBB disruption after cerebral I/R injury.
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