Circular RNA circPTK2 regulates oxygen-glucose deprivation-activated microglia-induced hippocampal neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1 beta signaling

摘要

Oxygen-glucose deprivation (OGD)-activated microglia contribute to neuronal apoptosis via releasing pro inflammatory cytokines, and some miRNAs have been reported to be involved in this process. Circular RNAs (circRNAs) have been reported to function as miRNA sponges, but it remains unknown whether and how circRNAs contribute to OGD-activated microglia-induced neuronal apoptosis. Here, we investigated the function and relationship of miR-29b and circFTK2 in OGD-activated microglia-induced neuronal apoptosis. We found up regulation of TNF-alpha and IL-1 beta, and downregulation of miR-29b in OGD-activated microglia. miR-29b inhibited OGD-activated microglia-induced neuronal apoptosis. Meanwhile, miR-29b promoted SOCS-1 expression, and suppressed JAK2/STAT3 signaling. In addition, inhibition of JAK2/STAT3 signaling downregulated IL-1 beta expression, while upregulation of miR-29b or SOCS-1 also inhibited IL-1 beta production. IL-1 beta was confirmed to be an apoptosis inducer of hippocampal neurons. Moreover, either SOCS-1 upregulation or blockade of JAK2/STAT3 signaling suppressed OGD-activated microglia-induced neuronal apoptosis. These data suggest that miR-29b inhibits OGD-activated microglia-induced neuronal apoptosis via inducing SOCS-1 expression, blocking JNK2/STAT3 signaling, and inhibiting IL-1 beta production. circPTK2 was confirmed to inhibit miR-29b expression in OGD model by directly binding to miR-29b. Function assay showed that circPTK2 regulated microglia-induced neuronal apoptosis via sponging miR-29b. Collectively, these findings suggest that circPTK2 regulates OGD-activated microglia-induced neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1 beta signaling. (C) 2019 Elsevier B.V. All rights reserved.