LncGBP9/miR-34a axis modulates macrophage M1/M2 polarization to affect spinal cord injury repair via STAT1/STAT6 and SOCS3

Background: Acute spinal cord injury (SCI) could cause mainly two types of pathological sequelae, the primary mechanical injury, and the secondary injury. The dysregulation of macrophage polarization to a pro-inflammatory (M1) or an anti-inflammatory phenotype (M2) might cause the failure to post-SCI repair.Methods: In the present study, we conducted SCI model in Balb/c mice and observed the deregulation of M1/2 macrophage polarization after SCI; by bioinformative analyses, lncRNA lncGBP9 and SOCS3 have been regarded as potent regulators of the macrophage polarization after SCI. Mouse bone marrow-derived macrophages (BMDMs) were isolated and identified.Results: In M1 macrophages, lncGBP9 silence significantly decreased p-STAT1 and SOCS3 expression and protein levels, as well as the production of IL-6 and IL-12; in M2 macrophages, lncGBP9 overexpression increased SOCS3 expression and protein levels while suppressed p-STAT6 levels and the production of IL-10 and TGF-β1, indicating that lncGBP9 overexpression promotes the M1 polarization of macrophages. In lncGBP9-silenced SCI mice, the M2 polarization was promoted on day 28 after operation, further indicating that lncGBP9 silence revised the predominance of M1 polarization at the late stage of secondary injury after SCI, therefore improving the repair after SCI. Conclusions: In macrophages, lncGBP9 sponges miR-34a to rescue SOCS3 expression, therefore modulating macrophage polarization.