LncRNA MALAT1 promotes high glucose-induced inflammatory response of microglial cells via provoking MyD88/IRAK1/TRAF6 signaling

Although a large number of studies have confirmed from multiple levels that diabetes mellitus (DM) promotes cerebral ischemic reperfusion (I/R) injury, but the precise mechanism is still unclear. A cerebral I/R injury model in diabetic rats was established. The neurological deficit scores and brain edema were monitored at 24 and 72 hours after injury. The peri-infarct cortical tissues of rats were isolated for molecular biology detection. The rat primary microglia and microglia line HAPI were cultured to establish the cell model of DM-I/R by high glucose (HG) and hypoxia-reoxygenation (H/R). The endogenous expression of MALAT1 and MyD88 was regulated by the transfection with pcDNA-MALAT1, si-MALAT1 and si-MyD88, respectively. The cerebral I/R injury model in diabetic rats had more severe neuronal injury as shown by the significantly higher neurological deficit scores and an obvious increasing brain edema at 24 and 72 hours after injury. Moreover, the microglia were activated and induced a large number of inflammatory cytokines TNF-α, IL-1β and IL-6 in the peri-infarct cortical tissues during cerebral I/R injury associated with DM. The expression of MALAT1, MyD88, IRAK1 and TRAF6 protein were significantly up-regulated by DM-I/R in vitro and in vivo. Furthermore, the HG-H/R-induced MALAT1 promoted the inflammatory response in microglia via MyD88/IRAK1/TRAF6 signaling. Our results suggested that MALAT1 mediated the exacerbation of cerebral I/R injury induced by DM through triggering the inflammatory response in microglia via MyD88 signaling.