IL-1{beta}-induces NF-{kappa}B and upregulates microRNA-372 to inhibit spinal cord injury recovery

In this study we have shown that in cultured human neural stem cells (hNSC), IL-1β reduced the expression of both KIF3B (kinesin family member 3B) and NOSIP (nitric oxide synthase-interacting protein), two key modulators for restricting inflammation and promoting neuronal regeneration. The induction of microRNA-372 (miR-372) by IL-1β is specifically responsible for the inhibition of KIF3B and NOSIP. The 3'-untranslated regions (UTRs) of both KIF3B and NOSIP contain targeting sequences to miR-372 that directly inhibit their expression. Moreover, we found that the expression of miR-372 was stimulated in hNSC by IL-1β through an NF-B binding site at its promoter region. Finally, stable overexpression of miR-372 inhibitor in hNSC rescued the IL-1β-induced impairment as shown by significant improvements in tissue water content, myeloperoxidase activity, and behavioral assessments in SCI rats. These findings suggest a critical role of miR-372 in inflammatory signaling and pinpoint a novel target for the treatment of acute SCI. NEW & NOTEWORTHY Our data demonstrate that IL-1β can impair the functional recovery of neural stem cell transplant therapy for spinal cord injury (SCI) treatment in rats. This effect is dependent on microRNA-372 (miR-372)-dependent gene repression of KIF3B and NOSIP. Therefore, specific knockdown of miR-372 may provide benefits for SCI treatments.
Source: Journal of Neurophysiology - Category: Neurology Authors: Tags: Research Articles Source Type: research