Interfering with PTBP1 expression promotes anti-inflammatory macrophage polarization alongside altered activity of the miR-124/p38MAPK pathway.

Modulating the polarization phenotype of macrophages offers significant potential for treating central nervous system damage. Polypyrimidine tract binding protein 1 (PTBP1) is an indispensable RNA-binding protein that participates in nearly all stages of RNA maturation. However, the role of PTBP1 in macrophage polarization remains underexplored. This study aimed to investigate the effects of PTBP1 on macrophage polarization and elucidate the potential mechanisms. Immunostaining techniques were employed to evaluate the expression of PTBP1 in macrophages infiltrating spinal cord injury and cerebral ischemic zones. PTBP1 siRNA was utilized in lipopolysaccharide-induced RAW264.7 cells to interfere with PTBP1 expression. The effects of PTBP1 inhibition on phenotypic and metabolic alterations during macrophage polarization were examined. RNA-sequencing analysis was employed to detect differentially expressed genes. Quantitative reverse transcription polymerase chain reaction, western blotting, and bioinformatics technology were conducted to validate underlying mechanisms. PTBP1 was highly expressed in M1-like macrophages infiltrating the injured spinal cord and cerebral ischemic zones. Elevated nuclear accumulation of PTBP1 coincided with lipopolysaccharide-induced activation in RAW264.7 cells. Inhibiting PTBP1 downregulated M1-like genes and upregulated M2-like genes. PTBP1 knockdown was associated with altered metabolic markers, including reduced ROS and increased ATP production, suggestive of a potential shift in metabolic phenotype. Moreover, PTBP1 inhibition enhanced mature miR-124 expression and correlated with reduced activation of the downstream p38MAPK pathway. In conclusion, PTBP1 represents a potential therapeutic target for modulating macrophage polarization phenotypes. PTBP1 inhibition promoted an anti-inflammatory macrophage phenotype, correlating with modified miR-124/p38MAPK signaling and glucose metabolic reprogramming.