SIX1 aggravates the progression of spinal cord injury in mice by promoting M1 polarization of microglia

Spinal cord injury (SCI) can cause permanent loss of motion or sensation. After the initial physical damage, the body responds with inflammation, which paradoxically can worsen the injury. This study focuses on how a protein called SIX1 affects inflammation after SCI in mice. Microglia, which are immune cells in the spinal cord, can either promote (M1) or reduce (M2) inflammation. The researchers found that SIX1 increases after SCI and seems to push microglia towards the M1 type, worsening inflammation. By blocking SIX1, the researchers were able to shift microglia towards the M2 type, reduce inflammation, and improve recovery in mice with SCI. This suggests that targeting SIX1 could be a new way to treat SCI.

• 1
  SIX1 expression increases in microglia following SCI in mice and is positively correlated with the M1 microglia marker iNOS and negatively correlated with the M2 microglia marker Arg1.
• 2
  Knockdown of SIX1 promotes locomotor function recovery by enhancing M2 microglia polarization in mice with SCI.
• 3
  SIX1 enhances the transcription of VEGF-C in LPS-stimulated BV2 cells by downregulating EZH2, and VEGF-C promotes M1 polarization and inhibits M2 polarization by binding to VEGFR3.