LncRNA Gm4419 contributes to OGD/R injury of cerebral microglial cells via IκB phosphorylation and NF-κB activation.

Ischemic stroke is one of major causes of adult morbidity. Recent studies have shown that over-activated microglial cells play a critical role in aggravating cerebral oxygen glucose deprivation/reoxygenation (OGD/R) damage by releasing excessive inflammatory cytokines. However, the involving mechanisms are not distinct yet. Long non-coding RNAs (lncRNAs) have been reported to in participate in lots of complicated biological processes. Our understandings of the relationship between lncRNAs and OGD/R injury are largely limited. In this study, we demonstrated that a lncRNA Gm4419 functioned as a crucial mediator in the activation of NF-κB signaling pathway, causing neuroinflammation damage during OGD/R. Gm4419 was abnormally up-regulated in OGD/R-treated microglial cells. We found that the high level of Gm4419 promoted the phosphorylation of IκBα by physically associating with IκBα, therefore, led to increased nucleus NF-κB levels for the transcriptional activation of TNF-α, IL-1β and IL-6. In addition, we also demonstrated that knockdown of Gm4419 functioned as NF-κB inhibitor in OGD/R microglial cells, showing that down-regulation of Gm4419 had protective role against OGD/R injury. In summary, Gm4419 is required for microglial cell OGD/R injury though the activation of NF-κB signaling. Thus, Gm4419 appears to be a promising therapeutic target for ischemic stroke.