Abstract
Macrophages can be polarized towards either a classically activated pro-inflammatory (M1) state, or alternatively towards an activated anti-inflammatory (M2) state. M1 cells are activated by ligands of toll-like receptor (TLR) or interferon (IFN)-γ and have a toxic effect, whereas M2 cells are activated by interleukin (IL)-4, IL-10, and IL-13 and have a regenerative effect in vitro and in vivo. Previously studies have shown that these cells play an important role in the inflammatory responses following spinal cord injury (SCI). Mechanistically, the role of PTEN in the regulation of macrophage polarization has yet to be fully elucidated. In the present study, we first evaluated the expression of PTEN in macrophages after SCI. We found that PTEN expression was accumulated in the macrophages after the SCI surgery. Knock-down of PTEN or inhibition of phospho-PTEN with bpV(pic) in RAW264.7 cells resulted in increased M2 polarization and decreased M1 polarization. In a rat model of SCI, grafts containing bpV(pic) reduced spinal tissue cavitation and promoted locomotor improvement, while combining grafts of bpV(pic) and acellular spinal cord (ASC) scaffolds showed a better effect. Moreover, grafts containing bpV(pic) enhanced M2 polarization and decreased M1 polarization in the macrophages during SCI. Thus, we have established that PTEN is critical for the polarization of macrophages and the functional recovery of SCI. Targeting PTEN enhances the macrophages towards to M2 polarization and promoting the functional recovery in SCI, and this suggest that PTEN may be a future therapeutic target for SCI treatment.